According to the U.S. Centers for Disease Control and Prevention, prediabetes is a serious health condition in which blood sugar levels are higher than normal, but not high enough to meet the threshold for type 2 diabetes. If diagnosed early, experts say, lifestyle changes such as weight loss and regular exercise can prevent or delay the development of type 2 diabetes and the increased risks it poses for heart disease, stroke, kidney failure and nerve damage.

Because the incidence of type 2 diabetes in the U.S. population (6.7 per 1,000 adults in 2018) has not changed significantly since 2000, it’s likely that individuals with prediabetes are not getting diagnosed and treated soon enough to prevent it from progressing. Johns Hopkins Medicine researchers analyzed electronic health records and insurance claims data to better understand patients with prediabetes in the Johns Hopkins Health System, and then used that information to recommend improvements in prediabetes care applicable to all medical institutions.

In their paper published March 2 in the Journal of General Internal Medicine, the Johns Hopkins Medicine researchers analyzed data from more than 3,800 patients. They found that 13% were formally diagnosed with prediabetes, referred to a nutritionist or prescribed metformin, a medication used to prevent the development of type 2 diabetes.

The research team, led by Eva Tseng, M.D., M.P.H., assistant professor of medicine at the Johns Hopkins University School of Medicine, evaluated the follow-up care that patients with prediabetes received over a five-year period, including whether they had repeated laboratory testing of their A1C level (the measure of a person’s average blood glucose, or blood sugar over the previous three months). Patients with prediabetes, they explain, have an A1C of 5.7 to 6.4. A normal A1C is below 5.7.

The researchers also determined if patients were diagnosed and medically coded for prediabetes, and if they were referred for nutrition therapy or started on metformin therapy.

Tseng says her team’s findings are similar to what previous studies by researchers outside Johns Hopkins have shown.

“Six percent of the patients evaluated developed diabetes within 12 months, which is similar to other studies,” Tseng says. “But these are people who we can potentially prevent from developing type 2 diabetes. Our results show that we have considerable room to improve in the identification and care of people with prediabetes within our health system and likely in many other places across the United States.”

Tseng recommends that patients be appropriately screened for prediabetes, and if diagnosed, begin discussing options for treatment with their providers.

“We want to make sure patients are aware they have this diagnosis and know of some basic steps they can take to address prediabetes,” Tseng says. “We hope to create a standardized dialogue about treatments, such as the U.S. Centers for Disease Control and Prevention’s National Diabetes Prevention Program, starting metformin and seeing a nutritionist.”

Tseng and her colleagues plan to use their findings to guide the continued improvement of prediabetes care for the health system. This model of care can then be used by other health systems.

This study was funded by the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases. The researchers do not have any conflicts of interest.

People with prediabetes were significantly more likely to suffer a heart attack, stroke or other major cardiovascular event when compared with those who had normal blood sugar levels, according to research being presented at the American College of Cardiology’s 70th Annual Scientific Session. Researchers said the findings should serve as a wake-up call for clinicians and patients alike to try to prevent prediabetes in the first place.

“In general, we tend to treat prediabetes as no big deal. But we found that prediabetes itself can significantly boost someone’s chance of having a major cardiovascular event, even if they never progress to having diabetes,” said Adrian Michel, MD, internal medicine resident at Beaumont Hospital-Royal Oak, MI, and lead author of the study, which he said is one of the largest to date. “Instead of preventing diabetes, we need to shift focus and prevent prediabetes.”

Prediabetes is a condition in which the average amount of sugar in the blood is high but not high enough to be diagnosed as Type 2 diabetes. While Type 2 diabetes is a well-known, leading risk factor for heart attack, stroke and blockages in the heart’s arteries, the role of prediabetes has been less clear. Yet prediabetes is fairly common. The U.S. Centers for Disease Control and Prevention estimates that 34 million Americans–just over 1 in 10–have diabetes, and another 88 million–approximately 1 in 3–have prediabetes.

This study revealed that serious cardiovascular events occurred in 18% of people with prediabetes compared with 11% of people with normal blood sugar levels over a median of five years follow-up. The relationship between higher blood sugar levels and cardiovascular events remained significant even after taking into account other factors that could play a role, such as age, gender, body mass index, blood pressure, cholesterol, sleep apnea, smoking and peripheral artery disease.

“Based on our data, having prediabetes nearly doubled the chance of a major adverse cardiovascular event, which accounts for 1 out of 4 deaths in the U.S.,” Michel said. “As clinicians, we need to spend more time educating our patients about the risk of elevated blood sugar levels and what it means for their heart health and consider starting medication much earlier or more aggressively, and advising on risk factor modification, including advice on exercise and adopting a healthy diet.”

Of particular concern was the finding that even when patients in the prediabetes group were able to bring their blood sugar level back to normal, the risk of having a cardiovascular event was still fairly high. Events occurred in just over 10.5% of these patients compared with 6% of those with no diabetes or prediabetes.

“Even if blood sugar levels went back to normal range, it didn’t really change their higher risk of having an event, so preventing prediabetes from the start may be the best approach,” Michel said.

This single-center, retrospective study included data from 25,829 patients treated within the Beaumont Health System in Michigan between 2006 and 2020. Patients were then split into either the prediabetes or control group based on at least two A1C levels five years apart; the control group included patients who maintained a normal hemoglobin A1C during the study. A total of 12,691 patients and 13,138 were included in the prediabetes and control groups, respectively. Participants ranged in age from 18 to 104 years. All patients were followed for the 14-year study period and researchers used international classification of disease codes or diagnostic codes to determine whether a major adverse cardiovascular event occurred.

The relationship between prediabetes and events were strongest among males, Blacks and people with a family history of cardiovascular disease or personal risk factors for heart disease. People who were overweight had the highest rates of cardiovascular events among all patients, even more than those who were obese, which is something Michel said needs to be studied further.

Prediabetes is thought to play a role in heart health because elevated glucose levels in the blood can damage and cause inflammation within the vessels. This causes injury to the vessels in the body and can lead to narrowing of the vessels and ultimately cardiovascular injury, Michel said.

The study findings are an important reminder for adults to know their blood sugar numbers, especially as prediabetes usually has no symptoms. As with diabetes, prediabetes is diagnosed based on results from blood sugar tests, including an A1C, which reflects someone’s average blood sugar for the past two to three months; a fasting plasma glucose test, which measures your blood sugar after not eating or drinking for at least eight hours beforehand; and/or an oral glucose tolerance test, which checks how well the body processes sugar after drinking a sweet drink given by the clinician. Prediabetes is suspected with an A1C between 5.7-6.4%, fasting blood sugar of 100-125 mg/dl, or an oral glucose tolerance test of 140-199 mg/dl, according to the American Diabetes Association.

More research is needed to validate these findings.

People with prediabetes, whose blood sugar levels are higher than normal, may have an increased risk of cognitive decline and vascular dementia, according to a new study led by UCL researchers.

For the study, published in the journal Diabetes, Obesity and Metabolism, researchers analysed data from the UK Biobank of 500,000 people aged 58 years on average, and found that people with higher than normal blood sugar levels were 42% more likely to experience cognitive decline over an average of four years, and were 54% more likely to develop vascular dementia over an average of eight years (although absolute rates of both cognitive decline and dementia were low).

The associations remained true after other influential factors had been taken into account – including age, deprivation, smoking, BMI and whether or not participants had cardiovascular disease.

People with prediabetes have blood sugar levels that are higher than usual, but not high enough to be diagnosed with type 2 diabetes. It means they are more at risk of developing diabetes. There are an estimated five to seven million people* with prediabetes in the UK.

Lead author Dr Victoria Garfield (UCL Institute of Cardiovascular Science and the UCL MRC Unit for Lifelong Health & Ageing) said: “Our research shows a possible link between higher blood sugar levels – a state often described as ‘prediabetes’ – and higher risks of cognitive decline and vascular dementia. As an observational study, it cannot prove higher blood sugar levels cause worsening brain health. However, we believe there is a potential connection that needs to be investigated further.

“Previous research has found a link between poorer cognitive outcomes and diabetes but our study is the first to investigate how having blood sugar levels that are relatively high – but do not yet constitute diabetes – may affect our brain health.”

In the study, researchers investigated how different blood sugar levels, or glycaemic states, were associated with performance in cognitive tests over time, dementia diagnoses, and brain structure measured by MRI scans of the brain. Each of these measures were limited to smaller subsets of the Biobank sample (for instance, only 18,809 participants had follow-up cognitive tests).

At recruitment all of the UK Biobank participants underwent an HbA1c test, which determines average blood sugar levels over the past two to three months. Participants were divided into five groups on the basis of the results – “low-normal” level of blood sugar, normoglycaemia (having a normal concentration of sugar in the blood), prediabetes, undiagnosed diabetes and diabetes. A result between 42-48 mmol/mol (6.0-6.5%) was classified as prediabetes.

The researchers used data from repeated assessments of visual memory to determine whether participants had cognitive decline or not. Though absolute rates of cognitive decline were low, people with prediabetes and diabetes had a similarly higher likelihood of cognitive decline – 42% and 39% respectively.

Looking at dementia diagnoses, researchers found that prediabetes was associated with a higher likelihood of vascular dementia, a common form of dementia caused by reduced blood flow to the brain, but not Alzheimer’s disease. People with diabetes, meanwhile, were three times more likely to develop vascular dementia than people whose blood sugar levels were classified as normal, and more likely to develop Alzheimer’s disease.

Senior author Professor Nishi Chaturvedi (UCL MRC Unit for Lifelong Health & Ageing) said: “In this relatively young age group, the risks of cognitive decline and of dementia are very low; the excess risks we observe in relation to elevated blood sugar only modestly increase the absolute rates of ill health. Seeing whether these effects persist as people get older, and where absolute rates of disease get higher, will be important.

“Our findings also need to be replicated using other datasets. If they are confirmed, they open up questions about the potential benefits of screening for diabetes in the general population and whether we should be intervening earlier.”

Among 35,418 participants of the UK Biobank study who underwent MRI brain scans, researchers found that prediabetes was associated somewhat with a smaller hippocampus and more strongly associated with having lesions on the brain (white matter hyperintensities, WMHs) – both associated with age-related cognitive impairment.

The researchers said that some of these differences could be explained by elevated blood pressure, as those participants taking antihypertensive medication were likely to have more WMHs and smaller hippocampal volume. Rather than the treatment having an adverse effect on the brain, the researchers said use of such medication might be an indicator of earlier untreated high blood pressure.

People with prediabetes can reduce their risk of developing type 2 diabetes by eating a healthy, balanced diet, being more active, and staying at a healthy weight.

Large study supports a focus on healthy lifestyle changes as findings show that older adults deemed “prediabetic” seldom progress to full diabetes

Older adults who are classified as having “prediabetes” due to moderately elevated measures of blood sugar usually don’t go on to develop full-blown diabetes, according to a study led by researchers at Johns Hopkins Bloomberg School of Public Health.

Doctors still consider prediabetes a useful indicator of future diabetes risk in young and middle-aged adults. However, the study, which followed nearly 3,500 older adults, of median age 76, for about six and a half years, suggests that prediabetes is not a useful marker of diabetes risk in people of more advanced age.

The results were published February 8 in JAMA Internal Medicine.

“Our results suggest that for older adults with blood sugar levels in the prediabetes range, few will actually develop diabetes,” says study senior author Elizabeth Selvin, PhD, professor in the Department of Epidemiology at the Bloomberg School. “The category of prediabetes doesn’t seem to be helping us identify high-risk people. Doctors instead should focus on healthy lifestyle changes and important disease risk factors such as smoking, high blood pressure, and high cholesterol.”

Type 2 diabetes leads to a chronically excess blood level of glucose, which stresses organs including the kidneys, weakens the immune system, and damages blood vessels, promoting heart disease and stroke among other conditions. The prevalence of diagnosed type 2 diabetes in the United States has gone from less than one percent in the 1950s to more than 7 percent today–and researchers believe that the actual figure now, including undiagnosed diabetes, is over 12 percent. This sharp increase is due to the aging U.S. population and increased rates of overweight and obesity.

Doctors have used the concept of prediabetes–involving blood glucose levels that are higher than normal but not yet in the diabetic range–as an indicator of elevated diabetes risk in younger and middle-aged people. However, the utility of the concept in older adults–especially those 70 and older–has been less clear.

“It’s very common for older adults to have at least mildly elevated blood glucose levels, but how likely they are to progress to diabetes has been an unresolved question,” Selvin says.

To get a better picture of how older adults with prediabetes fare, Selvin and colleagues turned to the Atherosclerosis Risk in Communities Study. This large epidemiological cohort project, funded by the U.S. National Heart, Lung, and Blood Institute and including both Black and white participants, has been running at four U.S. medical centers, including Johns Hopkins, since 1987. For their prediabetes analysis, the researchers selected 3,412 ARIC study participants who had attended a follow-up visit during 2011-13–a time when the participants were between 71 and 90 years old–and did not have any history of diabetes. The researchers then looked at how measures of the participants’ blood glucose levels had changed at the next follow-up visit during 2016-17.

As expected, the researchers found that “prediabetes,” defined according to two different blood-test measures, was very common among the participants at the 2011-13 visit. Those with prediabetes, defined by moderately high blood levels of glucose following overnight fasting (the impaired fasting glucose test, or IFG), represented 59 percent of the initial sample, and those with prediabetes defined with a different blood test for glycated hemoglobin (HbA1c), represented 44 percent of the initial sample.

However, the results showed that only small numbers of the participants who had prediabetes in 2011-13 had developed diabetes by the time of the 2016-17 visit–8 percent of the IFG-defined prediabetics, and 9 percent of the HbA1c-defined prediabetics.

By contrast, 44 percent of the IFG group and 13 percent of the HbA1c group had improved enough by the 2016-17 visit that their test results were back in the normal range. Moreover, 16 and 19 percent of these two groups had died of other causes by the 2016-17 visit.

The results show that older adults with prediabetes, over intervals like the one in the study, are more likely to have lower blood sugar levels–or to die for other reasons–than to progress to diabetes.

“It appears that in older adults, ‘prediabetes’ is just not a robust diagnosis,” Selvin says.

“Our findings support a focus on lifestyle improvements, including exercise and diet when feasible and safe, for older adults with prediabetes,” says Mary Rooney, PhD, a postdoctoral fellow at the Bloomberg School and the paper’s first author. “This approach has broad benefits for patients.”

Selvin and her colleagues recommend that for older adults, physicians should focus their screening efforts on risk factors, such as hypertension, that are more useful in predicting illness and mortality in this population.

In people with prediabetes, there are six clearly distinguishable subtypes (clusters), which differ in development of the diseases, risk for diabetes, and development of complications. IDM

All prediabetes is not the same: in people in the preliminary stages of type 2 diabetes, there are six clearly distinguishable subtypes, which differ in the development of the disease, diabetes risk, and the development of secondary diseases. This is shown in a study by the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the University of Tübingen, Tübingen University Hospital and the German Center for Diabetes Research (DZD). The results have now been published in Nature Medicine. The new classification can help in the future to prevent the manifestation of diabetes or the development of diabetes complications through targeted prevention.

Diabetes is a worldwide pandemic. Since 1980, the number of people with diabetes has quadrupled worldwide. In Germany alone, 7 million people suffer from it. And the trend is still rising. By 2040, the number of people with type 2 diabetes could increase to as many as 12 million. But type 2 diabetes does not develop from one day to the next. People often go through a longer preliminary stage of diabetes, in which blood glucose levels are already elevated but people are not yet ill. “For people with prediabetes it has not been possible until now to predict whether they would develop diabetes and be at risk for serious complications such as kidney failure, or whether they would only have a harmless form with slightly higher blood glucose levels but without significant risk,” said Professor Hans-Ulrich Häring, who initiated the study 25 years ago. However, such a distinction is important for the targeted prevention of the metabolic disease and thus for counteracting the diabetes pandemic. Researchers from Tübingen have now achieved an important breakthrough. Using cluster analysis* in people with prediabetes, they have discovered six distinct subtypes with different diabetes risk. A differentiated classification of prediabetes and diabetes makes it possible to carry out individual and early prevention and therapy of diabetes and its secondary diseases in a way that is adapted to the development of the disease.

Prediabetes: Six different clusters identified

The research group led by Professor Häring and Professor Fritsche at the University Hospital in Tübingen has conducted detailed studies of the metabolism of people with prediabetes who are still considered healthy. The test persons (n=899) are from the Tübingen Family Study and the study of the Tübingen Lifestyle Program. They have repeatedly undergone intensive clinical, laboratory chemical, magnetic resonance imaging and genetic examinations in Tübingen over the past 25 years. Based on key metabolic parameters such as blood glucose levels, liver fat, body fat distribution, blood lipid levels and genetic risk, the researchers were able to identify six subtypes of prediabetes. “As in manifest diabetes, there are also different disease types in the preliminary stage of diabetes, which differ in blood glucose levels, insulin action and insulin secretion, body fat distribution, liver fat and genetic risk,” said first author Professor Robert Wagner from the DZD Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the University of Tübingen, summarizing the results of the study.

Three of these groups (clusters 1, 2 and 4) are characterized by a low diabetes risk. The study participants in clusters 1 and 2 were healthy. Slim people are the main members of cluster 2. They have a particularly low risk of developing complications. Cluster 4 consists of overweight people, whose metabolism is still relatively healthy. The three remaining subtypes (clusters 3, 5 and 6) are associated with an increased risk of diabetes and/or secondary diseases. People who belong to subtype 3 produce too little insulin and have a high risk of developing diabetes. People in cluster 5 have a pronounced fatty liver and a very high risk of diabetes because their bodies are resistant to the blood glucose lowering effect of insulin. In subtype 6, damage to the kidneys occurs even before diabetes is diagnosed. Here, mortality is also particularly high.

But can the classification into six prediabetes subtypes also be confirmed in other cohorts? To investigate this, the researchers extended the analysis to include almost 7000 subjects in the Whitehall II Cohort in London and there, too, identified the six prediabetes subtypes.

More targeted prevention measures

The researchers are already making further plans. “Next, in prospective studies, we will first seek to determine to what extent the new findings are applicable for the classification of individual persons into risk groups,” said Professor Andreas Fritsche of Tübingen University Hospital. If this is the case, people with a high risk profile could be identified early on and receive specific treatment.

About the study

These results are based on research conducted by the Diabetes Research Department at Tübingen University Hospital over the past 25 years to characterize people with an increased risk of diabetes. The study was funded by the German Research Foundation, the Federal Ministry of Education and Research and the State of Baden-Württemberg.

“One of the DZD’s goals is to develop precise prevention and therapy measures, i.e. the appropriate prevention or treatment for the right group of people at the right time. The combination of in-depth clinical and molecular research with state-of-the-art bioinformatics has made this internationally important result possible. The identification of subtypes in the preliminary stages of type 2 diabetes is an important step towards precision medicine in the prevention of diabetes and its complications,” says DZD Executive Director Prof. Martin Hrab? de Angelis.