On the Low Birth Weight Risk for Insulin Resistance

Altered PI3-Kinase/Akt Signalling in Skeletal Muscle of Young Men with Low Birth Weight
Original source: PLoS ONE 3(11): e3738
Authors: Christine B. Jensen, Malgorzata S. Martin-Gronert, Heidi Storgaard, Sten Madsbad, Allan Vaag, Susan E. Ozanne (corresponding author)
Publication date: November 17, 2008
DOI (digital document ID): 10.1371/journal.pone.0003738
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
Low birth weight (LBW), an indicator of stress or an adverse fetal environment, is associated with increased future risk of insulin resistance and type 2 diabetes. The investigators are reporting continuing research on a specific insulin signaling pathway may be altered in skeletal muscle of young adult men with LBW. This would help increase our understanding of the mechanisms of insulin resistance in this particular population.

Muscle biopsies were obtained from 20 healthy 19-yr old men who had been in the lowest 10% birth weight for full-term babies and compared them to 20 physically similar men of normal birth weight. The samples were checked for fasting blood glucose and insulin levels, and after four hours in which insulin-production was medically stimulated.

The researchers looked at several previously-unstudied proteins and pathways related to muscular function and muscular glucose metabolism to see if there was any difference between the two groups of men. They found significant differences in the levels of several proteins after insulin stimulation. Some of these differences seen in the LBW group are similar to those seen in patients with insulin-resistant Type 2 diabetes.

The authors conclude that these differences in skeletal-muscle response to insulin precede, and may contribute to, the development of whole-body insulin resistance and type 2 diabetes in men with LBW.


Reliability:
The tests were done on a small number of subjects and a small number of controls. The small sample could skew the results obtained. Also, these were spot observations. Longitudinal observation of these subjects (over a period of time) might give the researchers better information about whether or not insulin resistance progresses in this manner in these subjects.

Practical Applications:
This is one of a series in basic research of how diabetes may develop in specific populations.

In many areas, low birth weight is associated with maternal malnutrition and/or poor prenatal care -- which are further associated with low-income communities and minority communities. Type 2 diabetes is more common in these groups than in the general population. Proving a definite link and path may bring more interest in providing education, and medical and dietary services, to this high-risk group.

Ethics note:
Written informed consent was provided from all participants and approval was obtained from the regional ethics committee.

This synopsis was based on the entire article.

Are moderate-protein diets better than low-protein diets for people with metabolic syndrome?

Moderate carbohydrate, moderate protein weight loss diet reduces cardiovascular disease risk compared to high carbohydrate, low protein diet in obese adults: A randomized clinical trial

Original source: Nutrition & Metabolism 2008, 5:30
Authors: Denise A Walker Lasker (corresponding author), Ellen M Evans, and Donald K Layman
Publication date: 7 November 2008
DOI (digital document ID): 10.1186/1743-7075-5-30
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
This study compares the effectiveness of the standard USDA Food Pyramid diet with a higher-protein, lower-carbohydrate diet for weight loss in general, for fat loss in particular, and for lowering the blood-based indicators of cardiovascular risk and insulin resistance. A total of 50 people completed the testing, split between the two dietary approaches.

Both diets under test had the same amount of calories, with about 30% of total calories coming from fats. Carbohydrates supplied about 55% of the Food Pyramid diet group's caloric intake, and protein, the remaining 15%. The people assigned to this group were instructed to eat whole grains for their bread products. About 30% of the high-protein group's calories came from protein, with the remaining 40% coming from carbohydrates. (This is the same protein-carbohydrate-fat distribution advocated by the Zone Diet.) This group was instructed to eat primarily "high quality protein", including lean meats, dairy, and eggs. Both groups had similar amounts of fruits and vegetables in their daily diets. All subjects were instructed on portion sizes, dietary substitutions, how to weigh foods, and how to keep a food diary. There was no difference in exercise between the two groups.

Baseline measurements (weight, body fat percentage, cholesterol, and postprandial insulin) were taken at the start of the experiment. The subjects followed their assigned diet plans for four months, at which time the same measurements were repeated.

• The moderate-protein group lost about 5 pounds more per person than the USDA group, and more of their weight loss was from fatty tissues.
• Fasting glucose levels were unchanged, but fasting insulin levels decreased in the moderate protein group, while it increased in the USDA group. In addition, postprandial insulin levels dropped 85% for the protein group, but only 50% for the Food Pyramid group. (High plasma insulin levels are indicative of insulin resistance, which is often a predecessor to Type 2 diabetes.)
  
• There was a greater drop in total cholesterol in the USDA group than in the protein group. LDL ("bad") cholesterol dropped in the USDA group but rose in the protein group; on the other hand, HDL ("good") cholesterol dropped in the USDA group but rose in the protein group. The protein group also showed greater improvement in triglyceride levels than the USDA group. (High triglyceride levels are associated with increased risk of heart attack.)
  

Reliability:
The study was small scale, with only 50 people completing the four-month study. While the two groups of subjects were selected to be closely-matched, there is still opportunity for the results to be skewed. An initial run-in period put all subjects on as close to an even footing as possible before the trial started.
The authors are associated with an accredited university; the paper was published in a peer-reviewed journal.
Longer-term studies of larger groups may be needed to determine the long-term safety and effectiveness of high-protein diets.

The principal investigator (Denise A Walker Lasker) received funding from the National Cattleman’s Beef Association, The Beef Board and Kraft Foods. Both Beef associations have a vested interest in increasing protein consumption (in the form of beef).
The investigators have made no comparison between a higher-fat restricted-carbohydrate diet and a higher-protein restricted-carbohydrate diet.

Practical Applications:
The 30/40/30 protein/carb/fat (PCF) ratio is the basis of the Zone Diet. While this diet is higher in protein than traditionally advised for people with diabetes, recent publications suggest that this is not as high a risk as formerly perceived.

For further reading:
WebMD evaluates the Zone Diet
Wikipedia entry on the Zone Diet

This synopsis was based on the entire article.

Could antioxidants fight diabetes?

The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile
Original source: Nutrition Journal 2008, 7:29
Authors: Daria Brambilla, Cesare Mancuso, Mariagrazia Rita Scuderi, Paolo Bosco, Giuseppina Cantarella, Laurence Lempereur, Giulia Di Benedetto, Salvatore Pezzino, and Renato Bernardini (corresponding author)
Publication date: 30 September 2008
DOI (digital document ID): 10.1186/1475-2891-7-29
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
The authors discuss the use of antioxidant foods and supplements in the treatment of chronic disease. They are particularly interested in the effect of dietary antioxidants on the management of cancer and neurological and immune disorders. They are particularly interested in antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which may be directly affected by the presence of antioxidants in the diet. They believe these enzyme systems may efficiently reduce oxidative damage and minimize the progression of disease-related oxidative stress. The clinical effects of dietary antioxidants is still under debate. Along the same lines, the excess consumption or bioavailability of fat-soluble vitamins has been associated with increased incidence of cancer.

The concepts of "free radicals" and "oxidative stress" are defined, and are said to damage the body's proteins, DNA, and lipids (fats). The authors mention some of the pathways in which oxidative stress occurs and can be measured, how oxidation can affect the digestive and immune systems, and how micronutrient deficiencies can cause the immune system to be depressed. This includes the discussion of methods for determining how the human body uses vitamins, minerals, and antioxidants, how chronic and autoimmune diseases may be affected by oxidative stress, and how antioxidants -- both alone and along with other chemicals -- may affect the disease process.The authors caution that the potential benefit of using antioxidants to reduce this damage must be weighed against the possible damage they might cause if overused, and that a thorough understanding of how these nutrients act chemically, in the cellular environment, and on a person as a whole.

Reliability:
The authors are associated with the pharmacology departments of their universities. The issues discussed are related to the pharmacological properties of nutrients and nutrient supplements (nutriceuticals). This is a general article; while specific diseases, oxidants, and disease pathways are mentioned, no quantitative analysis is given. The authors are optimistic about the use of antioxidants in the management of chronic illnesses, but are concerned about people blindly adding antioxidant supplements before their effects are thoroughly tested.

Practical Applications:
While neurological disorders are given particular emphasis, that the authors touch on "chronic diseases" and "autoimmune disorders" suggests that their findings may be useful in the use of dietary supplements for both Type 1 and Type 2 diabetes. Better understanding of how oxidative stress affects diabetes, and controlled experiments using particular antioxidants, are both needed both to verify whether or not this will work for most people, and to determine what specific antioxidants and combinations should be taken.

For further reading:
Check the authors' bibliography for studies relating to specific diseases.

This synopsis was based on the entire article.

Adapting "quality of life" measures to a local audience

Evaluating the reliability, validity and minimally important difference of the Taiwanese version of the diabetes quality of life (DQOL) measurement
Original source: Health and Quality of Life Outcomes 2008, 6:87
Authors: I-Chan Huang (corresponding author), Jung-Hua Liu, Albert W Wu, Ming-Yen Wu, Walter Leite, Chyng-Chuang Hwang
Publication date: 28 October 2008
DOI (digital document ID): 10.1186/1477-7525-6-87
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
The authors' goal was to develop ways to measure Health-Related Quality of Life (HRQoL) in the Chinese language, primarily for use in Taiwan. They translated a standard survey (called DQOL) to measure diabetes-related HRQoL, put it to a test, and tried to find out where it worked and where it needed tweaking.

There are a number of standards for measuring HRQoL in general, and diabetes-related quality-of-life in particular. One issue is that even among the diabetes-specific surveys, there are differences: some look at quality of life based on energy, mobility, ability to function, and social aspects along with the issues of testing and maintaining control; others look at the effect of medical treatment and satisfaction with that treatment, as well as concern about eventual development of complications. In order to be meaningful, the surveys have to pose questions that have meaning within the culture in which they are presented, and which put the patient at enough ease to answer truthfully. (For example, questions about sexual activity will not be answered in a society where that discussion is taboo.) One aspect of this is rewriting the survey in the local dialect.

A major issue with health-related quality of life surveys is determining what the patient means, and way he perceives the care he is receiving, and what changes to his responses mean over the course of time. There are several methods of statistically analyzing these responses and comparing them to an "impartial" standard -- physical measurements of the patient's health.

The clinical measurements used to validate the survey included HbA1c (a measurement of average long-term blood glucose levels), blood glucose levels two hours after meals ("two-hour postprandial"), fasting blood glucose levels, and the presence of some of the most common complications of diabetes (neuropathy - loss of sensation; foot ulcers, infections, and amputations; cardiovascular issues such as heart disease; and cerebrovascular (brain circulation) issues such as stroke).

In addition, two other diabetes-related quality of life surveys were translated and made more appropriate to Taiwanese culture, and used to verify the results of the Taiwan-adapted DQOL and to make those results meaningful to researchers and public health professionals.

The authors discuss their methods of translating and localizing the DQOL, their analysis of the data, and the limitations of their research.

Reliability:
The authors are all professionals in either public health or medicine, and interested in how patients perceive their quality of life.
The sample used was relatively small, but of a reasonable size to test the effectiveness of the surveys being developed; however, all of the respondents were from the same health center in Taiwan, and only four had Type 1 diabetes. The authors also noted that this analysis was done over a cross-section of patients at one time, and one of the real strengths of measuring quality of life is how it is perceived to change over time.

Practical Applications:
This is a first step in being able to understand, from the Taiwanese patient's viewpoint, the effects of diabetes on his quality of life. Applying this information to medical practice will help improve the level of care, and the effect of care, provided to these patients.

This synopsis was based on the entire article.

Effects of adding a second drug to Metformin

Outcomes of adding second hypoglycemic drug after metformin monotherapy failure among type 2 diabetes in Hungary
Original source: Health and Quality of Life Outcomes 2008, 6:88
Authors: Gyorgy Jermendy, Diana Erdesz, Laszlo Nagy, Don Yin, Hemant Phatak, Sudeep Karve, Samuel Engel and Rajesh Balkrishnan (corresponding author)
Publication date: 31 October 2008
DOI (digital document ID): 10.1186/1477-7525-6-88
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
The authors' goal is to determine how well patients' blood glucose levels are controlled, and how the patients felt about their quality of life with diabetes, when metformin was not sufficient to control their diabetes and a second drug was added. The medical records of patients who had been on two oral diabetes drugs for at least a year were followed back for at least one year when they were on the two drugs, and going back as far as six months before the second drug was added. Other medical conditions that might affect the choice of medications, or that might need different medications, were tagged.

The goal of diabetes care was to achieve an HbA1c of under 6.5%. HbA1c is a long-term measure of average blood glucose levels; it is believed that sustained high blood glucose levels are the cause of many of the complications of diabetes. One issue that complicates this goal is that the HbA1c level includes the effects of unusually or dangerously low blood glucose -- hypoglycemia.

414 patients, average age 60 years, participated in this survey, in which they were asked about hypoglycemic incidents, satisfaction with their treatment, and overall health-related quality of life (HRQoL).

Hypoglycemic episodes were ranked as mild (little disruption to activities), moderate (requiring the to interruption of normal activities), or severe (requiring immediate medical assistance). The patients were also asked to report any swelling, weight gain, and digestive discomfort that might have occurred since starting the second drug. They were also given a standardized questionnaire to determine whether or not they took one, or both, drugs as prescribed.

27 percent reported hypoglycemic incidents, one third of that group reporting at least one moderate or severe hypoglycemic incident. Three-quarters of the patients did not meet their HbA1c goal after a year of therapy; many blamed their weight for this, though the surveys suggest it is more likely that this failure was because they were not taking their medications correctly. Reasons for not taking medications included side effects and the belief that the medications would cause them to gain weight. Patients who did not get their HbA1c below 6.5% were as a whole heavier than those who reached the goal, and they were less likely to be satisfied with the change in treatment. The participants felt that hypoglycemic incidents reduced their health-related quality of life; also, the longer they had diabetes, the lower their self-reported HRQoL.

Reliability:
The group of patients examined was relatively small, and because the individuals reported their issues themselves, it is possible that some did not admit to not using their drugs correctly, or to other issues that might affect the results of their care.

The results were published in a peer-reviewed journal, and the effectiveness of oral diabetes drugs is a hot issue. This study shows some possible reasons for why dual-drug therapy is not always successful.

It is important to note that all but one of the authors works for Merck, either as a direct employee or a paid consultant. Merck is the manufacturer of sitagliptin (Januvia), which is in a different class of oral diabetes drug from those used in the study (DP-4 inhibitors). The failure rates of both sulfonylurea and thiazolidinedione drugs used in the study could be used to build a case for the preferential use of Merck drugs Januvia and Janumet (Januvia plus Metformin) for diabetes management, which would be very profitable for Merck. Merck paid for the study.

Practical Applications:
The care protocols recently issued by both the American Diabetes Association and the European Association for the Study of Diabetes suggest either adding a sulfonylurea (a class of drug which helps the pancreas make more insulin) or moving directly to insulin injections if metformin by itself does not provide effective results. While some second-tier drugs such as Actos and Byetta were mentioned, the use of these and other classes of oral diabetes drugs (including DP-4 inhibitors such as Januvia) were considered more expensive and not as well-tested.

Another issue to consider is that the time-frames for changing ineffective therapy are much shorter in the current recommendations than those followed by the doctors in this study. Since diabetes is a progressive disease, it is possible that by the time the second medication was added, the disease had progressed too far for that medication to be effective.

For further reading:
New Major Changes in Recommendations for the Treatment of Type 2 Diabetes by ADA and EASD -- a synopsis of the new treatment recommendations from Diabetes In Control
Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy -- the abstract of the new treatment protocols, as published in Diabetologia

This synopsis was based on the entire article.

Primary Care Physicians as point-of-care for Type 2 diabetes

Family physician and endocrinologist coordination as the basis for diabetes care in clinical practice
Original source: BMC Endocrine Disorders 2008, 8:9
Authors: Alejandra Duran, Isabelle Runkle, Pilar Matía, Maria P de Miguel, Sofia Garrido, Emilio Cervera, Maria D Fernandez, Pilar Torres, Tomas Lillo, Patricia Martin, Lucio Cabrerizo, Nuria Garcia de la Torre, Jose R Calle, Jose Ibarra, Aniceto L Charro, and Alfonso L Calle-Pascual (corresponding author)
Publication date: 31 July 2008
DOI (digital document ID): 10.1186/1472-6823-8-9
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
The investigators looked at diabetes patients with peripheral circulation and capillary circulation issues and sought to find out whether there was any measurable difference in the results whether the patient was treated by a primary care physician (PCP) or an endocrinologist.

One of the issues surrounding diabetes care in Spain is that primary care physicians (PCPs) may not be as aggressive in treating multiple risk factors and signs of complications of diabetes as a hospital-based endocrinology team. A program in which PCPs are trained to address all these factors and to consult with the hospital-based team was instituted. This study attempts to evaluate the effectiveness of this program.

In the "Area 7" section of Madrid, Spain, 126 patients with Type 2 diabetes and peripheral circulation issues were studied over a 30-month period. After an initial three-month period of treatment by the Diabetes team at St Carlos Hospital, the patients were broken up into two groups: one to continue care at St Carlos, the other to return to their program PCPs for diabetes care. Nine patients moved out of district over the period of the study, leaving 117 patients from which to evaluate this program.

The investigators looked at the folloiwng markers as indicators of care effectiveness: HbA1c (%); Total Cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides; blood pressure; albumine-to-creatinine excretion ratio (ACR); body mass index (BMI) and waist circumference (WC); anti-aggregation treatment; and smoking status.

At the end of the follow up, no differences were found between the groups for the following counters:

• more than 37% of diabetic patients achieved a HbA1c <>
• more than 50% a ACR <>
• more than 80% reached low risk values for cholesterol, LDL cholesterol, triglycerides, and diastolic blood pressure
• more than 80% were on aspirin therapy against platelet aggregation
• 12% remained smokers.

On the other hand,

• less than 45% achieved a systolic blood pressure <>
• only 49% of the men and 30% of the women had a waist circumference of low risk.

The largest difference between the groups is that while 23% of the patients cared for by the diabetes care team achieved a BMI less than 25, less than 12% of the patients cared for by family physicians achieved this level. Neither of these results was considered satisfactory and were attributed to focus on risk factors other than overweight.

The investigators concluded that good metabolic control can be achieved at the primary care level, if the PCP coordinates patient care with the endocrinologist. This will result in better results than being treated by an untrained primary care physician without endocrinological support.

Reliability:
The study was small enough that it could be a pilot project -- evaluation of a small-scale implementation before bringing this program to all of Madrid, or to all of Spain. The follow-up time was 2.5 years, which is an intermediate timeframe. Two of the authors work at the St Carlos hospital and clinic; the third is associated with the evaluation of primary care in the "Area 7" section of Madrid. The research was published in a peer-reviewed journal, which suggests a level of reliability to the results.

Practical Applications:
Moving Type 2 diabetes follow-on care out to the primary care practitioner can simplify care delivery from the patient's point of view. It also allows the PCP to do a better job of treating the entire patient, rather than a single aspect of that patient's care. In addition, teaching PCPs more about diabetes, and giving them consultation access to endocrinologists, can improve both initial diagnosis and ongoing diabetes care.


This synopsis was based on the entire article.

How "Bedside Manner" affects Self Care in Type 2 diabetes

The emotional context of self-management in chronic illness - A qualitative study of the role of health professional support in the self-management of type 2 diabetes
Original source: BMC Health Services Research 2008, 8:214
Authors: John Furler (corresponding author), Christine Walker, Irene Blackberry, Trisha Dunning, Nabil Sulaiman, James Dunbar, James Best, Doris Young
Publication date: 17 October 2008
DOI (digital document ID): 10.1186/1472-6963-8-214
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
One role of health-care professionals is to support patients with regard to both the clinical and emotional aspects of living with diabetes. The authors of this study tried to find approaches to make these professionals more effective at this task. They asked patients with Type 2 diabetes how they took care of their diabetes and how their relationships with their support teams affected this. They looked at groups who had been telephoned by nurses in the patients' general practitioners' offices to "coach" them about their diabetes and encourage them to become more actively-engaged their own health care and in their relationship with their family doctors. Their goal is to make these nurses more effective in this mission.

A total of 52 patients, ranging in age from 50-80, were split into four focus groups. Most of the participants were either unemployed or retired, and had had at least one visit with a diabetes educator. There were two English-language focus groups, plus one in Arabic and one in Turkish -- the two main languages of lower-income immigrants in the Melbourne, Australia urban area.

The groups focused on the role of personal control of diabetes and how one's relationships with one's healthcare team influenced this.

The investigators found that overall, the English speakers tended to see diabetes as life-limiting, almost punitive, and requiring self discipline. Dietary changes were viewed in terms of sacrifice -- for example, "having to give up" one's favorite foods. They looked at their entire care team as separate but equally important entities. They were more likely to "shop around" to find professionals who would give them "the right answers"; they needed information to be able to exert control their conditions.

Arabic and Turkish speakers saw diabetes as an integrated part of life, possibly indicative of stress. They saw self-management techniques as part of an integrated effort to restore personal calm. Dietary changes were put in a positive light -- using higher-quality foods rather than lesser quality ones, for example. They also relied primarily on their relationship with their General Practitioner, expecting him to provide them with all the information necessary to care for themselves. When they attended education sessions, or saw specialists, it was only upon the strong recommendation of their primary care physicians.

The investigators saw in the English-speakers the emerging concept of "patienthood", and doctor-patient relationships evolving to the ideal of the actively-engaged patient. (This is the model that is fostered by medical professional societies and by health insurers.) In contrast, they felt there was a potential danger in being completely uncritical of one's primary care physician, with the potential for insufficiently aggressive care and poorer long-term outcomes. The authors believe their findings suggest that a patient will see better results if his or her health-care professionals take the time to understand their patients' social, cultural, and emotional contexts and work from there to help them develop an effective approach to self care.

Reliability:
The study size was very small. The authors note that several aspects of its design could have skewed the results, and their specific results are not applicable outside of the particular community studied. The authors are a multidisciplinary group of professionals in medical practice, medical education, public health, and patient advocacy. The research was published in a peer-reviewed journal. The information should be considered more as a start-off point for your own relationships with your health-care team -- or if you are a practitioner, your patients.

Practical Applications:
There are many reasons that one's social and cultural background can either help or hinder self-care. I've often stated -- and even blogged -- that being willing to learn about the beliefs and cultural contexts of others, and by using those contexts as a starting point, the information or discussion you provide will be more easily understood, more appropriate to that other person, and where health information is concerned, more likely to get a positive response. I am encouraged to see this approach, and hope that it will improve diabetes care not just in Melbourne, but throughout the world.

This synopsis was based on the entire article.

One theory of increased colon cancer risk in Type 2 diabetes

Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control
Original source: BMC Endocrine Disorders 2008, 8:12
Authors: Deepak Kejariwal (corresponding author), Karolina M Stepien, Tracy Smith, Hugh Kennedy, David A Hughes, and Mike J Sampson
Publication date: 10 October 2008
DOI (digital document ID): 10.1186/1472-6823-8-12
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
People with Type 2 diabetes are at greatly increased risk for developing colon cancer, but the reasons for this are not clear. One possible reason may be DNA damage and oxidative stress, which may or may not be related to high blood glucose levels. Telomeres are DNA repeat sequences at the ends of chomosomes that get shorter each time a cell divides. After a certain point, they become non-functional. This causes a chemical signal to go out to kill the cell, preventing the growth of tumors. If the chemical signal is missing, the cells will continue to divide and the chromosomes will become unstable. Eventually this instability and continued cell division can result in tumors. The loss of this signal is found in many cancers, including about half of all colorectal cancers.

Under oxidative stress, telomeres may shorten more quickly, and less accurately, than they might otherwise. The authors believed that the telomeres of people with Type 2 diabetes are more prone to the effects of oxidative stress than those without diabetes, and that the cells from their colons would show evidence of shorter telomeres, which would kick off a series of events leading to colorectal cancer.

People with lower-intestinal and colon disease were excluded from this study, as were those who took vitamins or fish oil. The patients controlled their diabetes by taking metformin, a sulfonylurea drug, both of those, or insulin. A total of 32 people were examined between the people with diabetes and the non-diabetic controls. None of the subjects were smokers. The diabetic subjects had A1c under 6.9% but were dealing with known complications of diabetes. Tissue samples were taken from the lower colon and examined for oxidative damage and telomere shortening.

There were no appreciable differences in telomere length between the two groups. However, the groups were small, and the greater number of people with diabetes taking aspirin, ACE inhibitors (anti-hypertension medication), and/or statins (to reduce high cholesterol levels) may have provided some level of protection. Other reasons a difference was not seen could be that the diabetic subjects were in good control of their blood glucose levels, and that 6.5 years may not be a long enough time with diabetes for the effects of oxidative stress and increased colon cancer risk to be measurable.

Reliability:
Two of the investigators associated with a University hospital. The research was published in a peer-reviewed journal. The sample size was extremely small, and though steps were taken to minimize its effects, this small a sample could cause a skewed set of results. The authors do suggest that further research is necessary to confirm or rule out their theory.

Practical Applications:
More research is needed to find out exactly why people with Type 2 diabetes are at higher risk of developing colon cancer, and ways of minimizing that additional risk.

This synopsis was based on the entire article.

Are adverse effects of some diabetes drugs related to their suppression of sex hormones?

Are the adverse effects of glitazones linked to induced testosterone deficiency?
Original source: Cardiovascular Diabetology 2008, 7:30
Authors: M. Carruthers (corresponding author), T. R. Trinick, E. Jankowska, and A.M. Traish
Publication date: 15 October 2008
DOI (digital document ID): 10.1186/1475-2840-7-30
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
The authors pose a theory that the various adverse effects of diabetes drugs in the class called "glitazones" -- including rosiglitazone (RGZ -- brand name Avandia) and pioglitazone (PGZ -- brand name Actos) -- may be related to a separate known action of these drugs -- their suppression of sex hormones. These side effects include heart disease, swelling, weight gain, and anemia.

Glitazones act on sex hormones by reducing the levels to which they are released and by making the body less sensitive to them. These sex hormones are responsible for directing new cell growth to become blood vessels, skin, muscle, and other types of structural cells, rather than fat cells. This might give further weight to an existing theory of how obesity might cause diabetes (called "Ungar's theory of the 'Lipocentric Pathway to Hyperglycemia'"(1)). The authors note evidence that low testosterone levels in men can cause a number of the same side effects that are being observed in diabetes patients treated with glitazones; furthermore, that diabetes and/or cardiovascular disease are often seen to develop where testosterone production has been suppressed in order to treat prostate cancer. Much of this can be tied to the abdominal weight gain related to low testosterone levels. Treatment with testosterone in these cases has been shown to reduce the side effects and lower the statistical occurrence of cardiovascular disease among patients showing a number of these metabolic symptoms.

The authors note a number of known effects of rosiglitazone and troglitazone (Resulin, which has been removed from the US market) on sex hormones and on the development and maturation of new body tissues.

The authors suggest that this hypothesis might be tested by double-blind, placebo-controlled clinical studies examining the endocrine profiles, and levels of sex hormones, in people with Type 2 diabetes both before and while/after being treated with a glitazone. Additionally, studies on treating diabetic men with testosterone might show us whether this might counteract (or at least lessen) the adverse effects of glitazones. They also suggest further research into exactly how glitazones inhibit sex hormones.

Reliability:
The authors are associated with a number of universities and medical research institutes throughout the world. The hypothesis was published in a peer-reviewed journal. The authors are posing a theory, rather than a statement of fact, and suggesting ways that others could determine whether or not their theory is correct.

Practical Applications:
If the theory is correct, and if administering testosterone to men can completely counteract the adverse effects of Avandia and similar medications, that would make Avandia a relatively safer choice to treat Type 2 diabetes than it is now.

For further reading:
(1) Roger H. Unger, MD Reinventing type 2 diabetes: pathogenesis, treatment, and prevention. Journal of the American Medical Association (JAMA), 2008;299(10):1185-1187.
Full text requires paide subscription.
First 150 words available free.

"Evidence-Based Medicine", Patient Pages, Journal of the American Medical Association (JAMA)

This synopsis was based on the entire article.

Merck analyzes Januvia safety studies

Safety and tolerability of sitagliptin
Original source: BMC Endocrine Disorders 2008, 8:14
Authors: Debora Williams-Herman, Elizabeth Round, Arlene S. Swern, Bret Musser, Michael J. Davies, Peter P. Stein, Keith D. Kaufman and John M. Amatruda
Publication date: 27 October 2008
DOI (digital document ID): 10.1186/1472-6823-8-14
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
The authors are trying to assess the safety and of sitagliptin (Januvia) by combining the results of 12 separate double-blind human trials of up to 2 years in duration. (Double-blind trials are ones in which neither the investigators nor the patients know who is getting the drug under test and who is getting an alternate therapy or no drug therapy. This helps keep the results unbiased.)

A total of 6139 patients were involved in the studies; 3415 were either given 100 mg Januvia per day or the equivalent dose of another oral anti-diabetic pill; 2724 were given a placebo (a pill that has no drug action to it). The shortest study ran 18 weeks (about 4 months) and the longest ran 2 years. The patients were either given sitagliptin (Januvia) alone, or with metformin (similar to Janumet), or as addition to other antidiabetic drugs such as metformin (Glucophage), sulfonylurea, pioglitazone (Actos), and/or rosiglitazone (Avandia). The patients not getting the Januvia were getting either a placebo or one or more of the above antidiabetic drugs.

A number of known adverse reactions and side effects were examined in both the sitagliptin groups and the various control groups. According to the abstract, the only significant side effect was an increase in patient-reported hypoglycemic events among those patients who were also taking sulfonylurea drugs. The definition of "hypoglycemia" was somewhat loose, not requiring the patient to test his blood glucose and add it to the report. The authors do examine the frequency of reports of nausea and stomach pain, pancreatitis, immune system suppression, nose and throat discomfort, skin reactions (hives, discoloration, redness, etc.), and swelling in the heart and chest. These adverse reactions were considered to be similar in frequency between those taking Januvia and those who were not. The reasons for other studies reporting different results were discussed and discounted. (In at least one case, it was one of the longer-term studies that was looking specifically for adverse effects.)

The authors conclude that Under most circumstances, sitagliptin is safe and effective compared to other oral antidiabetic medications.

Reliability: The research was published in a peer-reviewed journal. One of the authors is a medical doctor.

All of the authors work for Merck, or worked for Merck during the period the research was being done. Merck manufactures Januvia, so the authors have a bias towards proving this medication safe and effective.

While a large number of patient experiences were collated into this analysis, most of the component studies were very small in scale.

Since most of the studies aggregated in this analysis only went on for four to six months, it is easy to misinterpret the data as indicating the drug is as safe over two years as it is over four months. People taking drugs to manage Type 2 diabetes are likely to stay on the same drug for much longer than the two-year longest studies examined -- so there is a possibility that there will be side effects from long-term use that have not yet shown up in laboratory and clinical studies.


Practical Applications:
Based on the authors' analysis, Januvia -- for the short-term and intermediate term -- is as safe as other drugs used to manage Type 2 diabetes.

However, because the severe reactions and deaths that have been tied to other new drugs* didn't start showing up in the media until the drugs were out in the marketplace for more than five years, and being taken by tens of thousands of patients, it is probably premature to say that Januvia is safe to be taken by the everyone covered by the prescribing instructions for the entire length of time one might expect it to be used. As with any medication, discuss the pros and cons with your doctor, as well as any additional concerns and risk factors you might have. Untreated Type 2 diabetes can cause serious complications up to and including death.

*Avandia (rosiglitazone), made by Glaxo Smith Kline, is the most recent drug with this sort of safety issue.

For further reading:
Januvia prescription information for doctors: http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf
Januvia site for consumers: http://www.januvia.com/sitagliptin/januvia/consumer/index.jsp
Merck website: http://www.merck.com/
Drugs.com consumer information for Januvia: http://www.drugs.com/cdi/januvia.html
Drugs.com professional information for Januvia: http://www.drugs.com/pro/januvia.html

This synopsis was based on the provisional (online preprint) article.

Discovering and Preventing Type 2 Diabetes in New Mothers

Gestational diabetes mellitus: postpartum opportunities for the diagnosis and prevention of type 2 diabetes mellitus

Original source: Nature Clinical Practice Endocrinology & Metabolism (2008) 4, 552-558
Authors: Rhonda Bentley-Lewis (corresponding author), Sue Levkoff, Alison Stuebe and Ellen W Seely
Publication date: 9 September 2008
DOI (digital document ID): 10.1038/ncpendmet0965
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
This Continuing Medical Education (CME) course is aimed at obstetrician/gynecologists and primary care physicians, who take care of women before, during, and after childbirth. A woman who has had gestational (pregnancy) diabetes is at increased risk of developing Type 2 diabetes. The aim of this course is to look at the need to monitor these women in order to prevent, or to quickly diagnose, Type 2 diabetes following childbirth. This requires screening for diabetes at one or more points after delivery.

In current medical practice, there are a number of conflicting guidelines for diabetes screening after delivery: while the American Diabetes Association (ADA) suggests either fasting blood glucose measurement or an Oral Glucose Tolerance Test at 6-12 weeks after delivery, with follow-ups every three years if the tests are normal, or every year if the test indicates impaired glucose tolerance. The World Health Organization (WHO) suggests a single follow-up six weeks or longer after delivery. The American College of Obstetricians and Gynecologists has no specific recommendation for diabetes screening after delivery. As a result, many women who have had gestational diabetes do not get follow-up screening.

Beyond the differing guidelines, the authors suggest several reasons that women may not be receiving appropriate postpartum diabetes screening. These include confusion as to whether this should be done by the obstetrician or the woman's primary care physician, whether or not she had a postpartum visit with the obstetrician, and whether or not she was instructed to get this screening.

The authors suggest several known methods for minimizing the risk of developing Type 2 diabetes after childbirth, including diet and exercise, weight loss, breastfeeding, and the preventative use of oral antidiabetes medications.

The authors suggest both monitoring new mothers who have had GDM 6-12 weeks after birth, and continuing to monitor them regularly thereafter.

Reliability: The authors are medical doctors with additional qualifications in public health, women's health, and psychiatry, and are associated with top-name institutions. The course is presented in conjunction with a peer-reviewed publication; the information is well-documented and the source publications are also peer-reviewed.

Practical Applications: The goal of CME courses is for doctors to keep up with current research and medical practice, with the end result of improving their ability to keep their patients healthy. Vigilant screening and attention to other diabetes risk factors will keep these mothers healthier for longer periods of time, lessen their risk of complications of diabetes, and potentially provide healthier role models for their children.

For further reading: The article's bibliography section has a number of online sources for follow-on reading.

This synopsis was based on the CME version of the complete article.

Metabolic syndrome increases risk of heart attack and stroke

Effect of metabolic syndrome or type II diabetes mellitus on the occurrence of recurrent vascular events in hypertensive patients
Original source: Journal of Human Hypertension (2008) 22, 358–365
Authors: A L M Vlek, Y van der Graaf, W Spiering, F L J Visseren (corresponding author), SMART study group
Publication date: published online 14 February 2008
DOI (digital document ID): doi:10.1038/jhh.2008.5
Requires subscription? Not for this article
Publicly-available abstract: Yes

Synopsis:
People with high blood pressure and vascular disease (diseases of the blood vessels) are at increased risk for recurrences of vascular disease, and for developing additional cardiovascular diseases such as heart disease, stroke, peripheral artery disease, and aneurysms. This study aims to find out whether having metabolic syndrome, and/or Type 2 diabetes, increases those risks even further.

Over 2000 people who were part of the Second Manifestations of Arterial Disease study (SMART) were followed for up to 10 years afterward for death, strokes, and heart attacks. These were used to calculate the risks of cardiovascular disease for people with high blood pressure only, for high blood pressure and metabolic syndrome, and for people with high blood pressure and diabetes.

Of this group, patients with metabolic syndrome (but without diabetes) had higher rates of stroke, heart attack, and sudden deaths related to cardiovascular issues. Patients with Type 2 diabetes had even higher risks than those with metabolic syndrome (but without diabetes). The increased risk of people with metabolic syndrome was not explainable by diabetes.

Further lowering of blood pressure did not seem to reduce the increased risk of heart attack and stroke in patients with metabolic syndrome.

Because people with metabolic syndrome have been shown to have higher risk of cardiovascular disease, investigators suggest more attention should be paid to diagnosing metabolic syndrome and treating it aggressively.

Reliability:
A large number of people were observed over a relatively long period of time. The authors work in a university medical center. The research was published in a peer-reviewed journal. The results should be relatively reliable.

Practical Applications:
Patients and healthcare providers should pay more attention to identifying the signs of metabolic syndrome and treating it with diet, exercise, and drugs (where appropriate).

Health insurance and life insurance actuaries will want to account for this relationship in their risk tables when determining coverage and premiums.

This synopsis was based on the entire article.

A possible reason for increased risk of infection of obese people and those with Type 2 diabetes

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus
Original source: International Journal of Obesity (2008) Vol. 32, pp. 1407–1414
Authors: G R C Zilverschoon, C J Tack, L A B Joosten, B J Kullberg, J W M van der Meer and M G Netea (corresponding author)
Publication date: published online 22 July 2008
DOI (digital document ID): doi:10.1038/ijo.2008.109
Requires subscription? Not for this article
Publicly-available abstract: Yes

Synopsis:
Interleukin-18 (IL-18) is a signalling chemical (similar to hormones) that has a strong effect on stimulating interferon (IFN) release. It is produced by a number of different white blood cells and central nervous system cells. Interferon is an important chemical in fighting infections.

Higher levels of IL-18 have been shown to decrease abnormally large appetite and to improve insulin sensitivity. Interestingly, several studies have shown high levels of IL-18 in obese people with insulin resistance, and a recent study has demonstrated that a common version of the genes producing IL-18 is associated with a higher body mass index (weight) in people with type 2 diabetes or coronary heart disease. In addition, weight loss after bariatric surgery (such as gastric bypass or lapband) results in lowered blood concentrations of IL-18.

The investigators suspect that the cells of obese people and those with insulin resistant diabetes may have high levels of IL-18 because they do not respond as well to IL-18 as those of people of normal weight and who are not diabetic. To test this theory, they tested white blood cells of obese and Type 2 diabetes patients and compared them to those of lean, non-diabetic people, and measured their IFN production in relation to their IL-18 levels. They found that in the obese and the diabetic subjects, these cells respond poorly to IL-18 and produce less interferon. They also show impaired release of IFN after exposure to disease-carrying bacteria and fungi.

They conclude that the reduced response to IL-18 may be responsible for the increased susceptibility to infection among those who are obese or who have Type 2 diabetes.

Reliability:
The study was conducted with a small number of subjects: seventeen control subjects, eleven obese non-diabetic subjects, and fourteen subjects with Type 2/insulin-resistant diabetes. (The possibility of LADA or other autoimmune diseases was ruled out at the start of the study.) The smaller the number of subjects, the greater the possibility for skewed or atypical results. The research was published in a peer-reviewed journal, and the investigators are all associated with the a University Medical Center in the Netherlands. Based on the small number of subjects, the results should be considered to point in the direction of larger studies to confirm the investigators' results, as well as further research into why these cells have an impaired reaction to IL-18.

Practical Applications:
A confirmed pathway and reason for increased risk of infection among obese people and people with Type 2 diabetes could lead to therapy to reduce that risk and to better fight those infections that do occur. If insulin resistance and excessive appetite are also directly related to impaired IL-18 response, then improving that response could conceivably result in weight loss and improved insulin sensitivity as well.


This synopsis was based on the entire article.