Dysglycemia (or blood sugar dysregulation) isn’t a disease per se; rather, it is an umbrella term for blood sugar (glucose) that fluctuates above and/or below a normal level. Individuals that are experiencing such an inability to consistently sustain healthy levels of “glycemic control” could be in the transition between normality and diabetes or other disorders. Dysglycemic individuals with a tendency toward high blood glucose spikes often progress to developing diabetes within 4 years. On the other end of the blood glucose pendulum, asymptomatic hypoglycemia (low blood glucose) that goes undiagnosed and unnoticed by patients has been found to be associated with higher rates of all-cause mortality, including heart attacks. So it’s no wonder that medical research is focusing a great deal of attention on this “precursor condition” to determine whether it is a cause or symptom of disease, whether it could be better detected (and screened for), and if it could be treated so as to halt transition to more serious disease and morbidity.
Defining dysglycemia or dysregulation
As defined by leading medical organizations, including the World Health Organization (WHO), individuals with dysglycemia (or dysregulation) have impaired glucose tolerance (IGT) and impaired fasting glycemia (IFG). Other groups label an individual as dysglycemic if they test abnormal for IGT or IFG.
Generally healthy people can experience “occasional” dysglycemia, either sporadic high blood glucose (hyperglycemia) or low blood glucose (hypoglycemia) or both, but if the occurrences become more chronic in nature, then that dysglycemic condition may trend toward prediabetes, type 2 diabetes or other disorders including atherosclerosis, connective tissue disorders or vascular dementia. As we’ll discuss further, scientists are still trying to determine whether dysglycemia is a cause or symptom of those serious disorders.
Why is blood glucose important?
This report won’t review everything medically important about blood glucose: see these articles for more information:
Simplifying the science, if you’re healthy, your blood glucose level will rise and fall gently throughout the day, in part reacting to how you digest carbohydrates, which your gut breaks down into sugar (aka blood glucose) that is released into your bloodstream. As your blood glucose levels rise, your pancreas gets to work producing insulin, a hormone needed to move that glucose out of your blood and into your cells so it can be converted into energy. Any extra glucose that your body doesn’t need for energy at that moment is stored in the liver, and if your insulin levels drop, your body can tap that backup supply to keep energy levels nice and stable. This balance, in healthy people, is called glucose homeostasis.
The Centers for Disease Control and Prevention (CDC) has issued these targets (using a simple blood sugar meter, also called a glucometer) for “normal” blood glucose, but cautions that your targets may be different depending on your age, any additional health problems you have and other factors:
- Before a meal: 80 to 130 mg/dL.
- Two hours after the start of a meal: Less than 180 mg/dL.
Be sure to talk to your health care team about which targets are best for you. Your medical team may order one of several other available blood glucose tests, including the gold standard A1c test, which is more sensitive than testing your blood at home with a glucometer.
If it is found that your blood glucose levels fluctuate dramatically, or stay chronically high or low, the systems that regulate blood glucose may begin to malfunction and eventually deteriorate, leading to a host of disorders — most notably diabetes and cardiovascular disorders. Fortunately, if detected early, lifestyle modifications (together sometimes with medications) can moderate dysglycemia; see our later section on treatment options.
As we’ll discuss below, abnormally low blood glucose (hypoglycemia) is often just a mild abnormality; or, if it’s acute and severe, hypoglycemia is nonetheless a condition that is typically transient or episodic in nature and amenable to immediate treatment. On the other hand, abnormally high blood glucose (hyperglycemia) is the component of dysglycemia/dysregulation that appears to be the most concerning as it relates to chronic and in some cases irreversible disorders and diseases — especially if not well-managed and treated on a consistent long-term basis.
Hypoglycemia: When blood glucose levels fall
As we explained in our guide, What Is Hypoglycemia?, this low blood sugar condition can happen if you’ve gone too long without eating, or have certain relatively rare hormonal conditions or liver disease. However, it occurs much more commonly among individuals with diabetes — especially if they are on insulin therapy and take too much medication. Left untreated, hypoglycemia can lead to seizures or coma, and even death; so those with diabetes know to take a high-calorie drink or snack if they have symptoms (such as racing heartbeat, shakiness, sweating). If this doesn’t work, it’s important to get medical help right away. A general rule of thumb for low blood sugar in diabetic individuals is a reading lower than 70 mg/dL. However, this is just a rough guideline, and each person has a blood glucose level that is healthy for them and is determined by their doctor.
Hyperglycemia: When blood glucose levels rise and stay too high
While unhealthy eating and other lifestyle choices can bring on “sugar highs” that are temporary in nature, and usually benign, frequent high blood sugar is unhealthy and is most often a result of relative insulin deficiency or insulin resistance, a condition in which the actions of insulin on peripheral tissues — including skeletal muscle, liver, and adipose — are impaired. Put another way, if you have a normal level of “insulin sensitivity,” you likely will have a normal blood glucose level. However, if you lose that insulin sensitivity, your glucose is not as effectively “disposed of” (i.e., moved into cells), which means glucose homeostasis is impaired and blood glucose levels rise above normal. (It is now recognized, too, that hepatic glucose production and insulin-augmenting incretin hormones, secreted by the gut in response to intestinal nutrients, play an important role in fasting and postprandial glucose regulation.)
Hyperglycemia puts you at risk for several serious conditions:
- Diabetes: The most notable disease that results from insulin resistance and chronically high blood glucose levels is type 2 diabetes (T2D), although a 2018 clinical review explains that “some obese individuals avoid T2D by virtue of a supranormal B-cell response.” Diabetes, of course, carries with it risks for many other diseases, most notably cardiovascular diseases (CVD) — especially prevalent in this population if blood glucose is poorly managed. Diabetes can also lead to kidney failure, nerve damage and even blindness. (See our next section for more on how dysglycemia and diabetes may be on the same disease continuum or spectrum.)
- Heart disease: One reason that the high blood glucose flare-ups that constitute dysglycemia, even in individuals that don’t (yet) meet the clinical criteria for diabetes, is of such interest in the medical and scientific fields is the finding that when you combine T2D and its preceding state, impaired glucose tolerance (IGT) — designated together as dysglycemia in this 2020 paper, you increase the risk for CVD by two to four times. Moreover, the study authors note that “future morbidity and mortality of patients with coronary artery disease (CAD) is considerably higher in the presence of dysglycemia, including newly detected glucose perturbations. Nonetheless, T2D and IGT remain unrecognized in approximately two-thirds of coronary patients.”
- Obesity: Not only are chronic post-meal (diet-induced) glucose spikes an independent risk factor for non-communicable disorders such as diabetes, they also contribute greatly to obesity. What’s particularly fascinating is the more recent understanding that genes are not as responsible for obesity as is a lifetime of high glucose-stimulated insulin secretion. The time of day your insulin is put to its biggest test is after a meal — the postprandial period, when people with insulin resistance have difficulty processing carbohydrates. Even if your fasting glucose is normal, individuals with higher levels of two-hour plasma glucose have a higher risk of developing diabetes. (See our report on Postprandial Blood Sugar to learn more.)
- Lipid metabolism abnormalities: In a seemingly cyclic relationship, hyperglycemia can worsen lipotoxicity, which can then worsen glucotoxicity (the set of negative outcomes associated with high blood glucose).
- Circulatory disorders: Even unrelated to diabetes, hyperglycemia is a risk factor for kidney problems, vision problems and nerve damage — even if blood glucose, albeit above normal, is below the level deemed to represent diabetes.
- Reproductive issues: About one in six pregnant women worldwide have a form of dysglycemia. Blood sugar problems raise the risk of miscarriage and birth defects and increase the risk of death for the mother and child.
- Mental illness: A growing body of research links balanced blood sugar to mood regulation, and dysglycemia (recurrent episodes of either too many lows or highs) appears to contribute to affective disorders, according to a 2020 review. Both hypoglycemia-prone patients and those with hyperglycemia are known to be at greater risk for mood disorders. A 2018 study found that insulin resistance correlated with more pronounced depressive symptoms in a cohort of obese depressed youths; and a 2017 prospective study, known as the Whitehall II study, found positive associations between high sugar consumption and common mental disorders, concluding that sugar intake from sweet foods and beverages has an adverse effect on long-term psychological health. While confounding variables do cloud the clarity of the association between hyperglycemia and mental illness in most of these studies, the body of research does indicate a likely bi-directional increase in the risk between both conditions.
Dysglycemia and diabetes … together on one continuum?
While the WHO states that people with dysglycemia are at high risk of progressing to T2D, they also opine that “this is not inevitable.” The question is, though: Are dysglycemia and diabetes often on one and the same continuum, or spectrum, if you will? Many researchers and clinicians alike are coming to such a conclusion, viewing dysglycemia as akin to “pre-pre-diabetes.”
But even today, definitions of prediabetes vary: The American Diabetes Association defines prediabetes as having a blood glucose level of 5.7%-6.4%; (at 6.5% or higher, it’s diabetes) as measured by an A1c test; 100 mg/dl to 125 mg/dl on a fasting plasma glucose test (FPG); or 140 to 199 mg/dl on an oral glucose tolerance test (OGTT). The CDC estimates that 96 million American adults — more than 1 in 3 — have prediabetes, and 80% of them don’t know they have it. Without intervention, 37% to 70% are expected to develop diabetes within 4 years, a likelihood that is 4-12 times higher than the general, normoglycemic population.
How many more people could have dysglycemia that precedes prediabetes, and also not know it? Anybody’s guess, unfortunately.
The call/cry for better screening
The vast number of people that have undiagnosed prediabetes, diabetes AND dysglycemia preceding prediabetes begs the question, of course: can’t we do a better job screening for these disorders? The answer is complex.
Realize first that diabetes, in all its many types, subtypes and levels of severity, is an extremely complex disease set. (See our related article, What Is Latent Autoimmune Diabetes in Adults, of LADA?) As so aptly put in a 2019 Cleveland Clinic review, “At the crux of diabetes are dysfunction and death of beta cells, the primary defect from which diabetes emanates regardless of subtype as defined by current classifications. However, beta-cell dysfunction is but 1 of 11 known paths leading to hyperglycemia. Diabetes arises from the interplay among beta cells and genetics, insulin resistance, environmental factors, inflammation, and immunomodulation.” Not only is it complex, but diabetes is also a heterogenous disease; as the ADA states, “clinical presentation and disease progression may vary considerably.”
Glucose dysregulation, or dysglycemia, is also more heterogeneous than previously thought: even individuals considered normoglycemic by standard measures exhibit high glucose variability, as shown in a 2018 clinical study that used continuous glucose monitoring (CGM) to evaluate the frequency with which individuals demonstrate elevations in postprandial glucose, the types of patterns, and how patterns vary between individuals given an identical nutrient challenge. The authors of this study have, through extensive phenotyping, developed a model for identifying potential mechanisms of personal glucose dysregulation and built a webtool for visualizing a user-uploaded CGM profile and classifying individualized glucose patterns into glucotypes. (While this work is ongoing, several features of their model have been incorporated into the January app to help individuals learn about and take charge of their metabolic health, including delivery of real-time insights on how diet and exercise affect glucose levels.)
It seems clear, then, that diabetes can be identified anywhere along the spectrum of clinical scenarios — in seemingly low-risk individuals who happen to have glucose testing, in individuals screened based on diabetes risk assessment, and in symptomatic patients — but such testing is not as widespread, nor as sensitive, as it would need to be to detect a much greater number of cases — and undoubtedly there are cost-effectiveness issues at play as well. A 2016 opinion article poignantly summarized the “testing gap” that, unfortunately, exists in this medical realm where so many individuals become ill, suffer and can even die prematurely because the early stages of disease could not be diagnosed, even though the technology to do so is available:
“Screening for dysglycemia has remained a contentious public health proposition for almost two decades. Debates about whether or not, and in whom, to encourage screening have led to disparate guidelines from influential expert committees, which may have contributed to large gaps in receipt of testing among those eligible. Indeed, recent national data from the US showed that only half of those eligible by the US Preventive Services Task Force (USPSTF) or the American Diabetes Association (ADA) guidelines reported having a glucose test in the past 3 years.…The recent expansion of criteria for dysglycemia screening, to adults aged 40–70 years who are overweight or obese, by the USPSTF is a welcome step. However, the criteria still exclude normal-weight people with dysglycemia, a group that may be especially prevalent in some populations, such as those of Asian or sub-Saharan African ancestry.”
More recently, various organizations have undertaken to advance the identification and study of new screening algorithms. The American Association of Clinical Endocrinologists (AACE) has created a dysglycemia-based chronic disease (DBCD) multimorbidity care model consisting of four distinct stages along the insulin resistance-prediabetes-T2D spectrum that are actionable in a preventive care paradigm to reduce the potential impact of T2D, cardiometabolic risk and cardiovascular events. This group states the following in its 2018 opinion memo:
“The controversy of whether there is value, cost-effectiveness, or clinical benefit of diagnosing and/or managing the prediabetes state is resolved by regarding the problem, not in isolation, but as an intermediate stage in the continuum of a progressive chronic disease with opportunities for multiple concurrent prevention strategies. In this context, stage 1 represents “insulin resistance,” stage 2 “prediabetes,” stage 3 “type 2 diabetes,” and stage 4 “vascular complications.” This model encourages earliest intervention focusing on structured lifestyle change. Further scientific research may eventually reclassify stage 2 DBCD prediabetes from a predisease to a true disease state.”
Screening remains a dilemma in part because, as admitted in the 2022 ADA Standards of Care, the existing and most recommended diagnostic tests — FPG, 2-h PG during 75-g OGTT, and A1c — “do not necessarily detect diabetes in the same individuals.” And the complexity extends to treatment options: “The efficacy of interventions for primary prevention of type 2 diabetes has mainly been demonstrated among individuals who have impaired glucose tolerance (IGT) with or without elevated fasting glucose, not for individuals with isolated impaired fasting glucose (IFG) or for those with prediabetes defined by A1C criteria.”
Screening research and future opportunities
- Youth-onset type 2 diabetes (T2D) is on the rise worldwide, accounting for one in three cases of incident diabetes. Worse, the rising prevalence of early-onset T2D is known to correlate to other major chronic conditions on the rise in young people — e.g., non-alcoholic fatty liver disease and cardiovascular disease. Yet, as a 2022 study reviewed, “common clinical assessment of T2D risk in youth relies on body mass index (BMI), waist circumference, race/ethnicity, family history of diabetes, and for high-risk youth, fasting glucose levels. However, these assessments may have limited preventive utility due to low sensitivity (e.g., BMI) and because studies in adults have shown that appreciable β-cell dysfunction has already occurred by the time glycemia becomes impaired.” (These study authors have identified “metabolomic biomarkers” that appear to improve the predictive capacity of T2D precursors beyond usual risk factors and conventional biomarkers, but more replication studies still need to be done.)
- Concurrent cardiovascular incidents: A 2021 study done in Sweden has found that, looking at dysglycemia after acute myocardial infarctions (AMIs), “two thirds of the patients admitted with AMI with no known history of diabetes had disturbed glucose metabolism, in accordance with previous studies…and that A1c in the prediabetes range, but not OGTT, would add predictive value on the long-term outcome [if this result is] communicated with lifestyle advice.”
- Type 1 diabetes (T1D): While considered a predominantly genetic disorder, better screening at the earliest stages would likely improve outcomes. In a June 2022 study, the authors review recent studies focused not just on family history and genetic predisposition, but also environmental and metabolic biomarkers in the hopes of better predicting the development and progression of T1D — since “once a child becomes symptomatic, beta cell mass has already reached a critical threshold (usually a residual of 20–30% of normal amounts), thus representing only the very late phase of the disease.” The authors describe “two preceding asymptomatic stages” in which they believe early metabolic alterations could one day be detected.
- In Europe, several leading medical organizations are assessing the value of various scoring systems to better estimate the future risk of T2D, including the FINDRISC system, which a 2018 review calls “a pragmatic strategy [in that it] would be to screen all patients with FPG followed by OGTT only in patients with IFG, [thus] decreasing the demand for an OGTT [as a cost-benefit trade-off].
- In an interesting 2018 study from Japan, authors concluded that if you test for serum creatinine, you’d be able to diagnose many more cases of dysglycemia — and if you find dysglycemia “early,” before it has progressed to full-fledged T2D and/or cardiovascular disease, you would be in a much better position to treat those chronic disorders with lifestyle modifications: “Low serum creatinine concentrations were positively associated with both incident dysglycemia and incident T2D over a 6.7-year follow-up period, independent of other major risk factors for T2D including age, body mass index, alcohol intake, physical activity and family history of diabetes.”
Dysglycemia treatment options
If and when dysglycemia is detected, and your medical team determines that your clinical profile and test results indicate that you could progress to prediabetes and T2D, better overall metabolic health management strategies can produce favorable results.
- First and foremost, managing your blood glucose levels is key. See our report, What Is A1c?, to learn not only how to monitor your blood glucose with this gold standard test, but to get an introduction to other monitoring advances, including CGMs.
- How you treat dysglycemia should be determined by you and your medical team, but lifestyle interventions (see our report on Non-Pharmacological Treatments) abound, including:
- Maintain a healthy weight and eat well: Eating a colorful and varied diet of mostly vegetables, legumes, lean meats and fruits is important for all aspects of health. Eating smaller portions more frequently may help your blood glucose levels stabilize. High-fiber foods are also particularly beneficial for overall metabolic health and blood glucose management. There are tools that can show you what foods are more harmful to blood sugar than others. The Glycemic Index (GI) was developed to show how certain foods affect your blood sugar levels. When your blood glucose levels are too high, aim for foods with low or medium GI values, such as whole grains, fish, yogurt, sweet potatoes, most nuts and legumes. Another tool, Glycemic Load (GL), tells you how quickly a food causes glucose to enter the bloodstream and how much glucose you’ll get per serving. For more information on glucose-lowering diet strategies, see the complete January AI Journal and learn how to make a healthier pizza or the best smoothie, purchase the lowest-glucose oatmeal alternatives, find the healthiest types of cooking oil and so much more.
- Exercise: Consistent physical activity (unless your healthcare provider advises against it) can lower your blood glucose levels and reduce the risk of T2D by up to a staggering 50%. Exercise has been shown to improve insulin sensitivity and glycemic control, while reducing the risk of mortality, according to a consensus paper published by the American Diabetes Association.
- Mind your sleep hygiene and get the recommended 7 hours/night.
- Hydrate: Drinking more water helps remove the excess sugar through your urine.
- Limit alcohol: Alcohol disrupts your body’s process of using glucose for energy and it can negatively impact your blood glucose levels, whether they’re too high or too low.
- Your medical team may also suggest certain medication therapies — which we will not detail in this report: see the ADA Medications & Treatments guide for basic information, or this more comprehensive 2019 Cleveland Clinic overview.
If you have frequent blood sugar swings, you may have a condition called dysglycemia (or dysregulation). You probably know quite a bit about these blood glucose highs and lows, and what to do about them, if you’ve received a diagnosis of diabetes. But many of us “assumed healthy” individuals could have dysglycemia, too — which could either be relatively benign, or a sign that a more serious disorder is in its early stages. Swings down (hypoglycemia) can be mild or more serious, but are often straightforward to treat. Swings up (hyperglycemia) can also be mild, and largely benign, but in a very large number of cases in the U.S. and worldwide, hyperglycemia signals the distinct possibility, if not probability, that serious metabolic disturbances are beginning that could lead to diabetes and/or cardiovascular and other conditions, if left untreated. Fortunately, if caught early, dysglycemia can be treated or managed with the lifestyle modifications we outline in this report, supplemented if necessary by medications that your medical team can discuss with you.