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.

Vitamin D and Gestational Diabetes

Maternal Plasma 25-Hydroxyvitamin D Concentrations and the Risk for Gestational Diabetes Mellitus
Original source: PLoS ONE 3(11): e3753
Authors: Cuilin Zhang (corresponding author), Chunfang Qiu, Frank B. Hu, Robert M. David, Rob M. van Dam, Alexander Bralley, Michelle A. Williams
Publication date: November 18, 2008
DOI (digital document ID): 10.1371/journal.pone.0003753
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
There is increasing evidence that Vitamin D plays a role in maintaining stable blood glucose levels, but the studies directly examining circulating levels of 25-hydroxyvitamin D (25-[OH] D) are limited and inconsistent. This study aims to determine the association between levels of (25-[OH] D) earlier in pregnancy than previously examined, and the risk of the mother's developing gestational diabetes later on in the pregnancy.

A nested case-control study was conducted among 953 pregnant women. 57 had diabetes at the start of the study, and 114 women who were not diagnosed with GDM were selected as controls.

Blood samples were taken at 16 weeks gestation, with known time since last meal, and frozen at -80C until analysis. Per American Diabetes Association guidelines, participants were screened for gestational diabetes at 24-28 weeks gestation, using fasting blood glucose and an oral glucose tolerance test. The process used to measure 25-[OH] D levels produces a maximum 12% probability of error.

The results were categorized as sufficient, insufficient, or deficient.

The odds ratios were adjusted based on mother's age at conception, season of conception, diet, vitamin supplementation, mother's pre-conception body mass index, family history of Type 2 diabetes, physical activity, and whether or not the mother smoked.

The women who developed gestational diabetes tended to follow the known risk patterns: overweight, older, being non-white or Latino, and having a family history of diabetes. The heavier these women were, the lower their circulating levels of 25-[OH] D.

At 16 weeks' gestation, 25-[OH] D levels of the women who went on to develop gestational diabetes were, on average, 20% lower than those of the controls. This difference remained even when filtering out the known and suspected risk factors for diabetes. About one third of the women who developed diabetes, versus one seventh of the women who did not, had 25-[OH] D levels considered to be deficient.

Further analysis showed an inverse relationship between vitamin D levels and risk of developing gestational diabetes was observed and remained even after considering all the factors mentioned above.

Reliability:
The number of women studied was moderately large and restricted to women who sought prenatal care prior to the halfway mark in the pregnancy. The study was also limited to women who read and wrote English, and who planned to deliver at one of two study hospitals. This may or may not filter out less-affluent women in higher-risk populations.

A 12% error in the assay method may skew the results, despite statistical attempts to minimize them.

The authors submit that a single blood test for 25-[OH] D levels may not provide an accurate picture of the mother's levels of Vitamin D throughout the pregnancy; also, that some of the 25-[OH] D deficient women may have developed impaired glucose tolerance or gestational diabetes earlier in the pregnancy (but had not been screened for it). The authors would like to see a much larger study conducted to confirm (or refute) their findings.

Practical Applications:
If a firm relationship between 25-[OH] D and gestational diabetes (or diabetes in general) is confirmed, then lifestyle changes and dietary supplementation can be advised earlier in the pregnancy (or pre-pregnancy) to minimize the risks of developing gestational diabetes.

This study also contributes to the general body of research regarding Vitamin D metabolism and diabetes in general. There may be good reasons for people with diabetes, or at risk for developing diabetes, to screen for Vitamin D levels and to increase Vitamin D intake. [Please note that Vitamin D is a fat-soluble vitamin and that excess intake is not easily excreted from the body, so please consult your physician before adding additional vitamin D supplements to your diet.]


This synopsis was based on the entire article.

Can genetic risks accurately predict Type 2 diabetes?

Clinical Risk Factors, DNA Variants, and the Development of Type 2 Diabetes
Original source: New England Journal of Medicine Volume 359, Number 21
Authors: Valeriya Lyssenko, Anna Jonsson, Peter Almgren, Nicoló Pulizzi, Bo Isomaa, Tiinamaija Tuomi, Göran Berglund, David Altshuler, Peter Nilsson, and Leif Groop
Publication date: November 20, 2008
DOI (digital document ID): not available
Requires subscription? Yes
Publicly-available abstract: Yes

Synopsis:
The aim of this paper is to determine whether environmental and clinical risk indicators, genetic factors, or both can be used to predict whether or not a person will develop Type 2 diabetes.

The authors singled out 16 specific gene markers that might be used to predict risk or development of diabetes. They tracked those, plus known environmental and clinical risk indicators, for over 16,000 Swedish patients and over 2500 Finnish patients, for a median period of 23.5 years. They studied the effect of variations of the gene markers on insulin secretion and insulin action over this period of time.

Over the observation period, approximately 11.7% of the subjects developed diabetes. Variations in 11 of the genes studied were associated with developing diabetes, independent of other risk indicators. Variants in eight of those genes were specifically associated with impaired beta cell function.

Adding the genetic risk to the clinical and environmental indicators slightly improved the long-term ability to predict whether or not an individual would develop Type 2 diabetes. This predictive ability increased with the duration of the follow-up.

Reliability:
While a large population was observed, and the medium observation time was over 20 years, the abstract does not provide insight into the distribution of follow-up duration, to let us know whether the median is a statistically-significant number. The improved prediction ability turns out to be about 1.5% better than the accuracy without the genetic information, which may not be cost-effective at the present time.

Practical Applications:
Known genetic risk is sometimes an incentive for making lifestyle changes to reduce the other risks for developing diabetes.

If the full paper shows direct correlations between insulin secretion, insulin resistance, and genetic variations, then initial pharmaceutical therapy can be better targeted to the individual's needs.

This synopsis was based on the abstract only.

How does your body-fat distribution affect your risk of death?

General and Abdominal Adiposity and Risk of Death in Europe
Original source: New England Journal of Medicine Volume 359:2105-2120 November 13, 2008 Number 20
Authors: T. Pischon, H. Boeing, K. Hoffmann, M. Bergmann, M.B. Schulze, K. Overvad, Y.T. van der Schouw, E. Spencer, K.G.M. Moons, A. Tjønneland, J. Halkjaer, M.K. Jensen, J. Stegger, F. Clavel-Chapelon, M.-C. Boutron-Ruault, V. Chajes, J. Linseisen, R. Kaaks, A. Trichopoulou, D. Trichopoulos, C. Bamia, Ph.D., S. Sieri, D. Palli, R. Tumino, P. Vineis, S. Panico, P.H.M. Peeters, A.M. May, H.B. Bueno-de-Mesquita, F.J.B. van Duijnhoven, G. Hallmans, L. Weinehall, J. Manjer, B. Hedblad, E. Lund, A. Agudo, L. Arriola, A. Barricarte, C. Navarro, C. Martinez, J.R. Quirós, T. Key, D.Phil., S. Bingham, K.T. Khaw, P. Boffetta, M. Jenab, P. Ferrari, and E. Riboli
Publication date: November 13, 2008
DOI (digital document ID): (unavailable)
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
This article addresses the question of whether the risks of obesity are related to the distribution of body fat, rather than the existence of fat excess body weight alone.

The investigators examined Body Mass Index (BMI), waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries over a period of almost ten years. The results were analyzed based on age at recruitment into the study, location at which they were entered into the study, height, educational level, whether or not the subject smoked, how much alcohol the person drank, and how physically active the person was.

The 1% of respondents with the highest and lowest energy intakes relative to estimated energy requirements were excluded from the study, as were respondents with a history of cancer, heart disease, or stroke.

"Normal" weight was considered to range from BMI 18.5 to BMI 25.0

The lowest risks of death based on BMI were at 25.3 for men and 24.3 for women. (This corresponds to the borderline between "normal weight" and "overweight".) After adjusting for this, absolute waist size and large waist-to-hip ratio were associated with greater risk of death. These last two correlations were stronger for people with lower BMI than for those with higher BMI, and stronger for men than for women.

One possible reason for the gender-related difference may be that overweight men tend to carry more fat in their midsections (visceral-fat) than equally-overweight women. This is important because visceral-fat tissue secretes a number of chemicals (lipokines) that can cause or exacerbate a number of chronic diseases.

Interestingly, it was found that the reasons for increased risk of death changed depending on waist measurement: those people who died and who were simply overweight or obese had more deaths from circulatory issues than from other causes, whereas those who had more abdominal obesity tended to die from respiratory issues rather than from other causes. (This may be a confounding issue, related to the observation that smokers tend to have more abdominal fat than non-smokers of similar BMI, and that smokers have higher risk of dying from respiratory system issues. The authors note that there is a known association between abdominal adiposity and chronic bronchitis, but do not state if this is a smoking-related association or not.)

The researchers conclude that these data suggest that both high body weight and abdominal fat are associated with higher risk of death, and support the use of waist circumference and or waist-to-hip ratio in addition to BMI in assessing the risk of death.

Reliability:
This study followed a large number of people for a relatively long period of time, making the study population relatively reliable; however, high BMI is not always related to adiposity. Body-builders, as a noted example, can have BMI in the obese range, but body fat measurement by either bioelectrical measurement or water immersion will indicate extremely low body fat percentages. On the other hand, these people generally have waist measurements and waist-to-hip ratios that are significantly smaller than people of the same body mass index, but with greater percentages of body fat. They also tend to have higher metabolic rates, making them more likely to place in the highest caloric intake per kilogram of body mass; some people who fit in this category were probably excluded from the study for that reason.

Another consideration, noted briefly by the investigators, is that there are a number of chronic diseases that were not excluded from the study. Some of these (such as Type 2 diabetes) affect, or are affected by, body weight and weight distribution. These could also affect the relative risks of death of the population observed.

Practical Applications:
The use of waist measurements and waist-to-hip ratios, in conjunction with BMI, can assist doctors and public health professionals in assessing individual and community health risks.

The authors' Figure 2, representing relative risk based on waist circumference and waist-to-hip ratio, shows a standardized risk of 1.0 for men at approximately 93 cm (about 36"), 0.94 waist-to-hip ratio (36" waist corresponding to about 39" hip), and for women at approximately 77 cm (about 30") waist size, 0.79 waist-to-hip ratio (30" waist corresponding to about 38" the hip). These measurements are lower than the standards currently used for determination of risk (102 cm/40" for men, 88cm/35" for women). Interestingly, these measurements correspond to the largest "standard" reference clothing sizes (men's pants to jacket size 42, women to U.S. Misses size 16/European size 42) as expressed in the home-sewing pattern industry, or "true-to-size" in the ready-to-wear industry.

This suggests that an average person should be able to determine his or her risk based on off-the-rack clothing size.

For further reading:
Home-sewing pattern measurements:

• Simplicity Patterns (United States):
  
  • US measurements
  • European measurements


• Burda Patterns (Germany):
  
  • US and European measurements

This synopsis was based on the complete article.

A possible genetic component of Type 2 diabetes

Variance of the SGK1 Gene Is Associated with Insulin Secretion in Different European Populations: Results from the TUEF, EUGENE2, and METSIM Studies
Original source: PLoS ONE 3(11): e3506.
Authors: Björn Friedrich, Peter Weyrich, Alena Stančáková, Jianjung Wang, Johanna Kuusisto, Markku Laakso, Giorgio Sesti, Elena Succurro, Ulf Smith, Torben Hansen, Oluf Pedersen, Fausto Machicao, Silke Schäfer, Florian Lang, Teut Risler, Susanne Ullrich, Norbert Stefan, Andreas Fritsche (corresponding author), Hans-Ulrich Häring
Publication date: 5 November 2008
DOI (digital document ID): 10.1371/journal.pone.0003506
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
The authors used a "classical candidate-gene approach" to examine genes that play a role in insulin secretion and their potential roles in the development of insulin-resistant diabetes. The gene they focused on is serum and glucocorticoid inducible kinase SGK1, which is encoded by the gene SGK on chromosome 6q23. The action of this gene is increased in the presence of corticoids and insulin, among other things, and seems to provide a molecular link between electrolyte activation and glucose stability. It also appears to play a role in both insulin signalling and insulin secretion and blood pressure.

The investigators looked at genetic variance in SGK, and potential associations with insulin secretory function, in two specific groups of people (the 725-person TUEF cohort and the 634-person EUGENE2 participants) whose diabetes risks had been examined for insulin secretion traits among those who were prediabetic. These were compared with the results of a study on an older, genetically-similar population (the 4457-person METSIM cohort) to determine whether their hypothesis was correct.

Insulin sensitivity and insulin production were measured using oral glucose tolerance tests (OGTT), measuring c-peptide levels or plasma insulin levels to determine insulin secretion, along with blood glucose levels to determine insulin sensitivity. BMI and waist-hip ratio were also measured in these populations. The patients were correlated to specific variations of one of four tagged alleles (rs9402571) of the SGK-1 gene.

There was no association of the specific tagged alleles with insulin sensitivity in either the TUEF screening population or in the EUGENE2 study, but the authors suggest that this expression of the gene's expression is based on BMI. They mention that the spot in which the SGK1 gene sits has been "associated with BMI progression in participants of the Framingham Heart Study."

On the other hand, the TUEF and EUGENE2 studies did report an increase in insulin secretion in lean patients with one specific variation of the rs9402571 allele. METSIM participants with this variation had a lower incidence of Type 2 diabetes. The authors suggest that this variation may protect against Type 2 diabetes, but that its effect may become blocked or blurred in overweight or obese individuals.

Their analysis suggests that the rs9402571 allele of the SGK1 gene is associated with altered insulin secretion and with Type 2 diabetes.


Reliability:
The authors are associated with accredited medical institutions and the results were published in a peer-reviewed journal. The subsets of the TUEF and EUGENE2 participants' data analyzed in the paper are relatively small. The correlation with an older population of similar genome poses a good initial check on the original hypothesis; the ongoing nature of the TUEF study (Tübingen Family Study) suggests that a more definitive correlation will be possible at some time in the future.

Practical Applications:
The developing discipline of genomics suggests that we might one day be able to base our healthcare on how our own particular genes work.

This synopsis was based on the entire article.

Mediterranean Diets: low-carb versus low glycemic load

Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss
Original source: Nutrition Journal 2008, 7:30
Authors: Joaquin Perez-Guisado (corresponding author), Andres Munoz-Serrano, and Angeles Alonso-Moraga
Publication date: 26 October 2008
DOI (digital document ID): 10.1186/1475-2891-7-30
Requires subscription? No
Publicly-available abstract: Yes

Enhancement of a modified Mediterranean-style, low glycemic load diet with specific phytochemicals improves cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia in a randomized trial
Original source: Nutrition & Metabolism 2008, 5:29
Authors: Robert H Lerman (corresponding author), Deanna M Minich, Gary Darland, Joseph J Lamb, Barbara Schiltz, John G Babish, Jeffrey S Bland, and Matthew L Tripp
Publication date: 4 November 2008
DOI (digital document ID): 10.1186/1743-7075-5-29
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
Both of these studies looked at variants of the Mediterranean Diet, followed over a period of 12 weeks (three months). The Spanish study emphasized the use of virgin olive oil as the primary source of dietary fat, green vegetables and salads as the primary source of carbohydrates, and fish as a primary source of protein. The US study is a follow-on to a previous study comparing a low-glycemic-load Mediterranean diet with added soy protein and phytosterols (plant-based fats) to the American Heart Association's diet plan. In this study, the diet is supplemented with plant-derived substances (phytochemicals) that they believe will improve insulin sensitivity and reduce cardiovascular and metabolic risk factors.

In the Spanish study, 31 obese people (BMI approximately 36) in their mid- to late-thirties were studied. They were not given caloric limits, but their diets included approximately 2 tablespoons of virgin olive oil (2 teaspoons per meal), 1-2 glasses wine daily (half at lunch and half at dinner),
green vegetables and salads to a maximum of 30 g carbohydrate per day, and unlimited protein. Non-nutritive sweeteners were allowed on this diet. Protein was divided into "fish" and "non-fish" (meat, fowl, eggs, shellfish and cheese), with "fish" and "non-fish" being consumed on separate days, and at least four "fish days" per week. In addition, subjects were allowed up to two cups of coffee or tea per day, and required to drink at least three liters of water per day. The subjects were given a standard multivitamin-and-mineral supplement and a calcium supplement; they were also asked to check their urine for ketones using ketostrips.

• Results: After 12 weeks, the subjects lost about 14 kg (30-35 lb), lowered their blood pressure (by about 15 points (millimeters mercury) systolic and 9 points diastolic), lowered their total cholesterol about 10%, significantly dropped their triglyceride levels (from about 218 down to 114 mg/dl), and reduced their fasting blood glucose level about 16 mg/dl. In addition, LDL ("bad") cholesterol levels dropped about 8%, and raised their HDL ("good") cholesterol about 9%. While the subjects were not heavy enough to have moved from "obese" to "overweight" in this time frame, the measured changes moved the patients' statuses from "prehypertension" to "normal blood pressure", from "prediabetic" to "normal", and from "high cholesterol" to "normal cholesterol". Based on the factors used to diagnose it, these subjects would be considered to no longer have metabolic syndrome. The researchers did not measure the beginning and ending percentages of body fat versus muscle mass, but their visual observation suggests that the weight lost was primarily fatty tissue.
• Limitations: The study had a number of limitations, including small size, short duration, highly-selected population, no measurement of total caloric intake, and the possibility that weight loss alone, as well as any of the factors of the program -- either by itself or in combination with others -- may have accounted for these changes. The authors suggest further study with a larger group of people, for a longer period of time, and also comparison with other low-carb diets.

The US researchers' initial viewpoint is that modern diets induce tissue inflammation, resulting in metabolic syndrome. They state that a number of active ingredients in medicinal plants target the pathways of this inflammation, and believe that the addition of these active agents to a low-glycemic-load adaptation of the Mediterranean diet can assist the body in repairing this damage. The US study included 49 patients with metabolic syndrome, average age 53 years, average BMI approximately 34. All subjects had high LDL cholesterol and triglycerides, and had at least two of the other signs used to diagnose metabolic syndrome (low HDL cholesterol, stage I hypertension or drug-treated hypertension, large waist size, and impaired fasting glucose. Half were put on a modified Mediterranean diet alone; the other half were put on the modified diet with the inclusion of phytochemical supplements. The two groups were split out in a way to minimize the initial differences between them.
In this version of the Mediterranean diet, wine was limited to 1 glass per day. Whole grains were allowed, but only one serving per day. Vegetables were mostly limited to very low glycemic load vegetables, with a maximum of one "occasional" serving of a small category of
phytochemical-rich vegetables with a moderate glycemic index (55-70). The only sweeteners allowed were stevia and low-glycemic agave nectar syrup.
The group receiving phytochemical supplementation received a nutritional supplement beverage (powdered) and supplement tablets. All subjects were required to engage in moderate aerobic exercise (at 70-75% target heart rate) for at least 2.5 hours per week. Food cravings, as well as food intake and satiety levels, were monitored (patient-generated logs and surveys). The results were analyzed, accounting for the effects of weight loss, consuming fewer calories, and consuming lower levels of carbohydrate.

• Results: At the end of 12 weeks, the diet-alone subjects lost about 5.7 kg (about 12.5 lb), and the supplemented group about an extra half-pound. While both groups showed lowered total cholesterol, LDL, and triglycerides, the group receiving the supplements saw greater reductions in these readings. Only the group with the supplements had increased HDL cholesterol. The group receiving the supplements were able to lower both systolic and diastolic blood pressure by about 6 points, while those receiving diet alone were only able to lower their systolic blood pressure, by about 4 points. Hemoglobin A1c (HbA1c), a measure of long-term blood glucose levels, went down in both groups, but fasting blood glucose did not drop in the group receiving supplements. Twice the number of subjects in the group receiving supplements were able to move from "having metabolic syndrome" to "normal".

Reliability:
The authors in the Spanish study are associated with the Genetics department of the University of Cordoba and do not report any conflicts of interest. Their bibliographic references are from peer-reviewed journals, mostly in the realm of nutrition.

The authors in the US study all work for the MetaProteomics, a research subsidiary of Metagenics, a company which produces and sells dietary plans, including a number of dietary supplements and meal replacement formulas, which it states will improve the health, weight,
and longevity of people with metabolic syndrome and cardiovascular disease. The MetaProteomics subsidiary is aimed at research into human proteins and how specific chemicals in foods are used by the human body. The bibliographic references are from peer-reviewed journals, and their source research is aimed more at finding the causes of cardiometabolic disease as well as specific chemicals that might lessen the probability of developing these diseases. As employees of a subsidiary of Metagenics, the authors' research is aimed at developing new products (both diets and supplements) for Metagenics to sell.

Both studies are limited in small sample size over short amounts of time; additionally, the Spanish study considers fewer variables.

There are significant differences in the two low-glycemic/low-carb "Mediterranean diets" studied: the Spanish study centers on healthy proteins and fats, while the US study aims more at trying to determine the effect of an anti-inflammatory diet and of the phytochemical
supplements the company sells.

Practical Applications:
Both versions of "Mediterranean diet", unsupplemented, showed favorable changes in cholesterol levels and blood glucose levels. The Spanish study showed greater changes in weight loss, blood pressure, triglycerides, and HDL cholesterol than the US study including supplements; however, the limitations of both studies does not indicate how effective either diet is at maintaining long-term health, or how safe they are over long periods of time.

Any highly-restrictive diet has its limitations, and even some less-restrictive diets may not be suitable for your personal medical conditions. Please consult your doctor and nutritionist before making any large-scale changes to your diet.

This synopsis and comparison was based on the full articles.

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.

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 disease and diabetes

Metabolic syndrome risk for cardiovascular disease and diabetes in the ARIC study
Authors: C M Ballantyne (correpsonding author), R C Hoogeveen, A M McNeill, G Heiss, M I Schmidt, B B Duncan and J S Pankow
Original source: International Journal of Obesity Volume 32, Supplement 2, pp. S21-S24
Publication date: May, 2008
DOI (digital document ID): doi:10.1038/ijo.2008.31
Requires subscription? Not for this article
Publicly-available abstract: Yes

Synopsis:
The investigators studied over 15,000 middle-aged Americans in four communities for a period of approximately ten years to try to determine the role of metabolic syndrome in the development of cardiovascular (heart and artery) disease and diabetes. The particular study is called Atherosclerosis Risk in Communities (ARIC).

Metabolic syndrome is diagnosed by the presence of three or more of the following characteristics: waist circumference greater than 40" in men or 35" in women; high triglycerides (over 150 mg/dl); low HDL or "good cholesterol" (less than 40 mg/dl in men or 50 mg/dl in women); high blood pressure (over 130/85 mm Hg); and high fasting glucose levels.

The investigators studied the numbers of those with and without metabolic syndrome to determine how much greater a risk someone with metabolic syndrome has of developing atherosclerosis, heart disease, stroke, or diabetes.

• ARIC participants who had metabolic syndrome were two to three times more likely to have coronary heart disease than those without, with the highest additional risk in black men and white women.
• The walls of the carotid arteries of persons with metabolic syndrome were about 5% thicker than those without.
• The increased risk of stroke for those with metabolic syndrome was an additional 35-40 cases per 10,000 person years.
• Of those participants with three or more indicators of metabolic syndrome, who did not have diabetes, those with obesity and/or elevated fasting glucose levels had significantly increased risk of developing diabetes.

Reliability:
This is a large study, conducted over a long period of time, and the article was published in a peer-reviewed journal. Both this, and the academic credentials of the authors, result in high levels of confidence in the results.

Further reading:
More information on the design of the ARIC study and publications based on information collected during the study can be found at the ARIC home page.

This synopsis was based on the entire article.