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.

Diabetes and Risk of death from coronary events

Diabetes Mellitus and Mortality after Acute Coronary Syndrome as a First or Recurrent Cardiovascular Event
Original source: PLoS ONE Vol. 3, No. 10
Authors: Richard M. Cubbon, Afroze Abbas, Stephen B. Wheatcroft, Niamh Kilcullen, Raj Das, Christine Morrell, Julian H. Barth, Mark T. Kearney (corresponding author), Alistair S. Hall for the EMMACE-2 investigators
Publication date: 22 October 2008
DOI (digital document ID): 10.1371/journal.pone.0003483
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
Diabetes has been associated with problems recovering from, and with higher risk of death from, acute coronary syndrome. The investigators were looking to find whether this increased risk was true for all persons with diabetes, or only for those persons with diabetes who already had cardiovascular disease, compared to people without diabetes (with, or without, diagnosed cardiovascular disease). The investigators wondered whether cardiovascular disease is diagnosed earlier in people with diabetes than in the general population, and if that early diagnosis, plus aggressive preventative treatment, reduced the risk of dying from acute coronary syndrome.

For the purposes of the study, "Acute Coronary Syndrome" covered unstable angina or myocardial infarction (heart attack). "Cardiovascular Disease" was devined as myocardial infarction, angina, stroke, peripheral vascular disease, or coronary revascularization (either the heart's circulatory system rerouting itself, or the need for stents, bypasses, or other surgical techniques to open or replace blocked blood vessels). Note that by these definitions, "acute coronary syndrome" is a subset of "cardiovascular disease".

The researchers looked at the data collected in the EMMACE-II observational study in 2003, which tracked just under 2500 patients. The investigators used the patients' previous medical records to split the patients into four groups: those without diabetes or previously-diagnosed cardiovascular disease; those without diabetes, but who had existing cardiovascular disease; those with diabetes but without a history of cardiovascular disease; and those with both diabetes and a history of cardiovascular disease. The data from these four groups were analyzed separately and compared.

The results showed that while patients with diabetes had an overall increased risk of death from acute coronary syndrome, the rates of death of patients with no history of cardiovascular disease were approximately the same, regardless of whether or not they had diabetes.

After adjusting for age and gender, there was still an increased risk of death for patients with diabetes and a history of cardiovascular disease over patients from the other three groups; however, when the results were adjusted for levels of Troponin I -- which was used to indicate how much of the heart muscle had died due to cardiovascular disease, the correlation between mortality and diabetes disappeared. This lack of correlation remained even when the investigators broadened or narrowed the definition of cardiovascular disease used in their analysis.

These findings suggest that the risk of dying from acute coronary syndrome may be related to the degree to which the heart's blood vessels have been blocked, and that the reduced degree of blockage in patients with diabetes, but no history of cardiovascular disease, may be related to aggressive preventative treatment that is not routinely offered to people without diabetes.

Reliability:
The authors are from accredited medical institutions and the research is published in a peer-reviewed journal. The size of the study is large enough to show potential trends and suggest directions for further research. The authors note limitations of the study include the absence of several key risk indicators (such as albuminuria -- protein in the urine -- and obesity) and details of any preventative therapy the patients may have received. They also note that patients with a history of previous cardiovascular disease are less likely to receive prescriptions for preventative drugs (such as statins and ACE inhibitors) than patients being discharged after their first acute coronary event, and because this is counterintuitive to standard practice, understanding the reasons for this difference would also help to quantify the differences in risk.

Practical Applications:
Understanding the true origins of the risks of death from acute coronary syndrome can help our doctors better treat us and help us reduce those risks to the greatest degree possible.

For further reading:
The British Cardiac Society Working Group definition of myocardial infarction: implications for practice -- abstract describing the EMMACE-II study.

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.

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.

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.