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The complications of type 2 diabetes — damage to the kidneys, nerves, eyes, and cardiovascular system — result from chronically high blood sugar.
While routine blood tests can provide a snapshot of blood sugar levels at one point in time, a more complete picture of long-term blood sugar control is obtained by measuring the extent to which sugar molecules are attached to hemoglobin, the oxygen-carrying protein found in red blood cells.
Measurement of this “glycated hemoglobin” reflects the total amount of sugar blood cells have been exposed to over the preceding eight to 12 weeks.
Clinical trials have shown that elevated, yet sub-diabetic, glycated hemoglobin levels increase risk for type 2 diabetes and cardiovascular disease. But although many studies have looked for genetic variants associated with type 2 diabetes itself, much less work has been done to uncover the genetic determinants of glycated hemoglobin levels.

Guillaume ParÃ© and colleagues from Harvard Medical School and Amgen, Inc., scanned the genomes of more than 14,000 apparently healthy (i.e. non-diabetic women) to look for SNPs that correlate with glycated hemoglobin. Their results, published online today in <a href="https://dx.doi.org/10.1371/journal.pgen.1000312" target="_blank" rel="noopener noreferrer">PLoS Genetics</a>, show that a variant in a gene never before linked to diabetes, HK1, is associated with glycated hemoglobin levels. Three other genes previously linked to diabetes and blood glucose concentration — GCK, SLC30A8 and G6PC2 — also harbored significantly associated variants.
According to the authors, the discovery of a link between the HK1 gene and glycated hemoglobin levels paves the way for further studies of the role of this gene in glucose metabolism and diabetes. The HK1 gene encodes the enzyme that carries out the first step of sugar breakdown in many cells throughout the body.
Together with the four variants, the researchers found to account for only a very small proportion of the total variance in glycated hemoglobin levels in the population — just 1.4%. Age, body mass index (BMI) and menopause status, on the other hand, explain about 9.5% of the variance.
Glycation of proteins in tissues other than red blood cells is thought to underlie the long-term complications of diabetes. The authors say it remains an open question whether the differences in glycated hemoglobin associated with the genetic variants identified in this study are paralleled in other parts of the body.
The SNPs associated with glycated hemoglobin levels are listed below by rsid#, gene, and the version associated with higher levels.
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Genetic Variants Linked To Blood Sugar Level

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Diabetics have to be worried about more than just their cholesterol when it comes to the health of their arteries. They also have to watch their blood sugar to help prevent the build up of fatty plaques that can block blood flow.
But new research from the Joslin Diabetes Center and Harvard Medical School shows that high blood sugar may be more dangerous to some diabetics than others.
Dr. Alessandro Doria and colleagues found that a genetic variant on chromosome 9 previously associated with coronary artery disease (CAD) risk in the general population has an even greater effect in diabetics with poor blood sugar control. These results, published online today in the <a href="http://jama.ama-assn.org/cgi/content/short/300/20/2389" target="_blank" rel="noopener noreferrer">Journal of the American Medical Association</a>, could someday help doctors identify people with diabetes who are at higher risk of CAD earlier, allowing them to aggressively target these patients for intervention.
People with diabetes are at least twice as likely as those without to have heart disease. Some studies suggest that middle-aged diabetics have the same high heart attack risk as people without diabetes who have already suffered a heart attack.

The first of two study groups was composed of 322 diabetics with coronary artery disease and 412 without. The researchers found that the risk for CAD was about the same in people with either the AA or AG genotype at rs2383206, even if they had poorly controlled blood sugar.
Having the GG genotype at rs2383206, however, increased the odds of CAD by about two-fold for diabetics with well-controlled blood sugar. And when high blood sugar was thrown into the mix, the odds of CAD for people with two Gs went up higher still — about four times compared to the lowest risk group.
In people with the GG genotype and a long history of high blood sugar, the odds of CAD were increased about seven times compared to diabetics with a history of well-controlled blood sugar.
(The study looked at rs2383206, which is available to 23andMe customers who were genotyped on the second version of our custom chip. But people who were genotyped on the first version can use rs2383207, the SNP we feature in the Health and Traits research report on Heart Attack, as a substitute. The G version is riskier for both SNPs.)
In a separate study group of 475 diabetics who were followed for 10 years, people with the AA or AG genotype at rs2383206 had the same risk of dying in general, or from cardiovascular disease in particular, regardless of their blood sugar. But for people with the GG genotype, the risk of death went up by a factor of two when blood sugar was not under control.
Both groups of diabetics Doria et al. studied were of European ancestry.
“While good glucose control is important for all people with diabetes, testing for this predisposing variant may help doctors identify patients for whom better control is an absolute necessity,” said Doria in a statement. The authors estimate that 30% of diabetics will have two Gs at rs2383206.
The probability of clinically significant CAD is about 30% for type 2 diabetics in general. The authors say this number could shoot up to 60% for diabetics with the GG genotype at rs2383206 and poorly controlled blood sugar.
The authors admit that this is a small study that will need verification. They also note that their findings are at odds with a <a href="https://www.ncbi.nlm.nih.gov/pubmed/18048406?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum" target="_blank" rel="noopener noreferrer">previous report</a> that found no difference between the risk conferred by SNPs in the 9p21 chromosomal region (where rs2383206 lies) in diabetic vs. non-diabetic subjects. Due to a number of methodological differences between the two studies, Doria et al say that no direct comparison of the results is possible.

Combination of Genetics and High Blood Sugar May Mean Extra Heart Disease Risk for Diabetics

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Recent genetic discoveries have taught researchers a lot about type 2 diabetes and identified particular genetic variants that can influence a person&#8217;s risk of developing the condition.
But two studies published this week in the New England Journal of Medicine conclude that genetic information still pales in comparison to factors like body weight, smoking, cholesterol levels, and other medical diagnostics when it comes to predicting who will develop the condition.
The papers are a reminder that although personal genomics promises to become a valuable supplement to preventive medicine, the information it provides shouldn&#8217;t be considered a replacement for regular check-ups and a healthy lifestyle. And though genetics certainly plays a role, diet, exercise and other environmental factors have a substantially greater impact on whether a person will develop type 2 diabetes.

Both studies looked at one-letter DNA variations known as single-nucleotide polymorphisms (SNPs) that have been linked to diabetes. The 23andMe Personal Genome Serviceâ„¢ provides information on nine diabetes-associated SNPs.
One study used data from the legendary <a href="http://www.framinghamheartstudy.org/">Framingham Heart Study</a>, which has followed three generations of participants over a period of 60 years, to show that inheriting a greater number of high-risk diabetes genes does increase a person&#8217;s chances of developing the condition. But when added to traditional measures of diabetes risk such as family history, body-mass index, fasting plasma glucose level, and blood pressure, a person&#8217;s genotype at the 18 SNPs studied did not significantly improve the researchers&#8217; ability to predict which of the 2,377 study participants became diabetic over a period of 28 years.
The other study, which looked at 16 SNPs in 16,061 Swedish and 2,770 Finnish subjects who had been followed for an average of 23.5 years, produced a similar result. The authors concluded that &#8220;common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes.&#8221;
However, because the physiological risk factors typically develop later in life (though they are becoming distressingly common in younger populations) the authors of the Framingham-based study suggest genetic information could be useful in motivating young people who have inherited a high diabetes risk to control their weight and take other preventive measures.
And research is bound to produce more knowledge about the genetic roots of diabetes. So in the not-too-distant future, a person&#8217;s genotype is likely to provide substantial predictive information beyond what is available from family history and physiology.

Diabetes Risk and Genetics

<img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2008/05/istock_000002904128xsmall.jpg" alt="istock_000002904128xsmall.jpg" class="right alignright" width="278" height="187" />The amount of sugar in the bloodstream must be tightly controlled. Too much can cause damage to nerves, blood vessels and organs. But too little sugar starves the body, especially the brain, of the energy it needs.
Fasting plasma glucose (FPG) levels are a measure of how well a person’s body can control blood sugar levels, a process that goes awry in diabetes. A report published online today in Science Express finds that FPG levels can be impacted by single-letter variations in genes known to be involved in blood sugar regulation.

<h6>Blood Sugar Levels</h6>
Physicians routinely test their patients&#8217; FPG levels to screen for diabetes and pre-diabetes. A high blood concentration of glucose after 8 to 10 hours of fasting indicates that a person’s ability to regulate blood sugar is impaired. High FPG levels are also associated with coronary heart disease mortality for both diabetic and non-diabetic individuals.
In order to identify genetic variants involved in blood sugar control, Nabila Bouatia-Naji and colleagues carried out a genome-wide association study to find single-nucleotide polymorphisms, or SNPs, correlated with FPG levels.
The most strongly associated SNP in an initial sample of about 650 non-obese French people. The same SNP was correlated with FPG levels in a second sample that included about 3,400 French people, approximately 5,000 Finns and a group of about 860 obese French children.
<h6>Additional Variants</h6>
Two other SNPs that were previously found to be associated with FPG were also found to be significantly associated with FPG levels in this study. The researchers believe that these genes affected by these SNPs affect the threshold level of glucose in the bloodstream, which triggers the secretion of insulin by the pancreas. The higher the threshold, the higher the blood glucose level will rise before insulin starts to regulate it.
“These sequences explain about 5 percent of the normal variation in blood glucose levels between otherwise healthy people,” explained Robert Sladek, one of the study&#8217;s senior authors.
When all three SNPs were considered together to create a score (each person has two copies of each SNP and gets one point for each “low FPG” version, meaning the score can range from 0 to 6), the researchers found that on average people who scored a 5 or 6 had FGP levels 0.24 mmol/l lower than people who scored 0 or 1.
“It’s important to know that a high blood glucose level, even within the normal and non-diabetic range, is a risk factor for early mortality,” said Dr. Philippe Froguel of Imperial College and CNRS. “Epidemiological studies have shown that 80 percent of the risk of cardiovascular disease is related to a blood glucose level just above the average.” The researchers propose that the three SNPs they identified &#8220;are likely to have a non-negligible impact on human health.&#8221;
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Genetic Factors Related to Blood Glucose

<img decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2008/02/coldguy.jpg" alt="coldguy.jpg" class="right alignright" />Modern lifestyles are often blamed for diseases such as obesity, <a href="https://www.23andme.com/topics/health-predispositions/fh/">high cholesterol</a>, heart disease and diabetes. But from an evolutionary standpoint those ailments may have roots in changes that occurred tens of thousands of years ago, when humans first left balmy Africa for more northerly climes.
Climate is already known to be partially responsible for the variations seen in body shape and size among humans. It&#8217;s no accident that Arctic Inuit tend to be short and squat while East African Maasai are long and lean.
<h6>Genetic Adaptations</h6>
Researchers at the University of Chicago recently hypothesized that climate might also have influenced genetic differences in metabolism.
“As some populations migrated out of Africa to much cooler climates, there would have been pressure to adapt to their new settings by boosting the processes that produce and retain heat,” said Anna Di Rienzo, a professor of genetics at the university.
A study published by Rienzo and her colleagues in today&#8217;s PLoS Genetics shows that genetic adaptations to colder climates do seem to affect susceptibility to many common metabolism-related disorders.

<h6>The Study</h6>
The scientists tested their idea by looking at SNPs in metabolism genes in 54 populations from around the world. They found that as a group, variations in these genes are correlated with climate measures such as temperature, humidity, and UV exposure.
Some of the variations that increased in frequency as people moved farther out of Africa have turned out to be harmful in the modern world. For example, the protein made by the FABP2 gene helps the body transport, absorb, and metabolize fats. A version of a SNP in this gene that is more prevalent in populations at higher latitudes causes the protein to bind fats more tightly. It has also been associated with increased insulin resistance, higher cholesterol and triglyceride levels, and more abdominal fat.
<h6>Adaptations for Colder Climates</h6>
But adaptations to colder weather that took place thousands of years ago don’t necessarily doom a population to a higher risk for disease today. A version of a SNP in the PON1 gene (which encodes a protein involved in dilation of blood vessels) is more common in populations from cooler regions. That version is associated with decreased risk for coronary artery disease, stroke, and heart attack.
According to the study’s authors, whether a variation increases or decreases risk for metabolic disorders will depend on exactly how the variation helped people deal with their new environment. For example, a variation in the LEPR gene probably helped early humans generate more body heat. Today this variant is associated with lower BMI. But the variation in the FABP2 gene discussed above, probably helped people stay warm by increasing BMI.
<img decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2008/02/climatpic22.jpg" alt="climatpic22.jpg" class="alignright" align="bottom" /> 
The frequencies of the two different versions of SNP rs662 in the PON1 gene are shown as a pie chart for each of the tested populations against a background map showing summer surface solar radiation. (From Hancock et al. (2008) Adaptations to climate in candidate genes for common metabolic disorders. PLoS Genet 4(2): e32. doi:10.1371/journal.pgen.0040032.g001)

diabetes — Page 2

Genetic Variants Linked To Blood Sugar Level

Combination of Genetics and High Blood Sugar May Mean Extra Heart Disease Risk for Diabetics

Diabetes Risk and Genetics

Genetic Factors Related to Blood Glucose

Climate Adaptations by Early Humans May Influence Disease Risk Today

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