You can still prevent or delay type 2 diabetes by losing weight—even a modest amount—with the help of dietary changes, stress reduction, and physical activity. Taking medication can also help. And reversing the process is key because type 2 diabetes can be a devastating disease.

The condition usually begins with insulin resistance, in which the fat, liver, and muscle cells do not use insulin properly. Eventually, the body needs more insulin than it can produce, causing blood glucose to rise.

Those elevated levels can lead to serious health issues if they are not managed properly. You may not even know you have prediabetes or diabetes—you can be symptom-free for years. But once the complications of diabetes start to occur, nearly every aspect of your health can be affected.

This is known as insulin resistance. As a result, the level of glucose in the blood rises. The pancreas initially responds by producing more insulin, but it will inevitably not be able to keep up, resulting in high blood glucose levels—a condition called hyperglycemia.

This can lead to such serious health issues as blindness, heart attack, stroke, kidney failure, and amputations of the feet, legs, or toes if it is not managed properly.

But prediabetes itself is a serious health issue. Each of those conditions raises the risk for serious issues, such as heart disease, stroke, and cancer. In people with prediabetes, some of the long-term damage to the blood vessels, heart, and kidneys may already be starting.

The first step is to know the risk factors, which can help determine whether or not you should be screened for the condition. Without screening, early signs of insulin resistance can be hard to identify—a person can have prediabetes for years without knowing it.

Obesity, an underlying cause of insulin resistance, is a major risk factor. A study published in found that participants who had obesity were about six times more likely to develop type 2 diabetes than those at a healthy weight, regardless of genetic predisposition; people who were overweight had 2.

Other common risk factors for prediabetes include being older than 45, exercising fewer than three times a week, having a parent or sibling with or a family history of type 2 diabetes, and giving birth to a baby that weighed more than 9 pounds.

Women who have polycystic ovary syndrome PCOS , a hormonal disorder, are also at higher risk for the condition. However, risk can be complicated for some people. Anam explains. Anyone who is not sure about their risk can take a simple online prediabetes test provided by the Centers for Disease Control and Prevention CDC.

Problems with insulin often start around puberty, says Yale Medicine endocrinologist Ania Jastreboff, MD, PhD , who treats both children and adults. But there are other factors, too. Pregnancy can also lead to struggles with weight for many women.

Gestational diabetes , which usually resolves after the baby is born, is another prediabetes trigger. Around menopause, changes in estrogen levels are associated with an increase in fat around the waist, which is considered a risk factor for diabetes.

In general, those who maintain good physical health as they age can avoid prediabetes. Heart disease can impact physical activity, as can the use of multiple medications, including glucocorticoids—steroids that, among other things, increase insulin resistance and glucose production by the liver, resulting in increased blood glucose levels.

They can also make people who take them feel hungrier, which leads to increased food intake and further contributes to hyperglycemia. Anam says. No FPG criterion for diagnosing prediabetes was offered.

The NDDG criteria for diagnosing diabetes were not equally sensitive. The American Diabetes Association ADA convened an Expert Committee to address this imbalance 7.

However, again there was an imbalance. Many fewer people with IFG subsequently developed diabetes compared with those who had IGT.

The ADA convened another meeting of the Expert Committee to address this issue 8 , 9. In response, the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation appointed an International Expert Committee that agreed with the invited expert panel regarding the diagnosis of diabetes if the A1C level were confirmed However, that committee also opined that because of the progressive continuum of risk of increasing glycemia below the diagnostic levels of diabetes for the subsequent development of diabetes, it was inappropriate to define a specific prediabetes risk group.

The ADA subsequently adopted the recommended A1C level for diagnosing diabetes but also included an A1C criterion of 5. The lower bound of the prediabetes criteria was based on modeling the estimated composite risk of developing diabetes and cardiovascular disease CVD using cross-sectional data from the — NHANES However, the glycemia of prediabetes is not independently associated with CVD 14 — Furthermore, in people who experience an acute coronary syndrome, the outcomes length of hospital stay, day readmission rate, acute pulmonary edema, month recurrent acute coronary syndrome, or mortality are no different between those with prediabetes A1C 5.

Rather, the association between prediabetes and CVD is due to the other risk factors for CVD that people meeting the glycemic criteria for prediabetes also have. Restricting the modeling to only the risk for developing diabetes might have influenced the prediabetes A1C criterion.

Although numerous studies have shown that glycemia is not an independent risk factor for CVD 14 — 21 , it certainly is for the development of diabetes. Similarly, the risk with the A1C IEP criterion of 6. Claims have been made that treating people with prediabetes with antihyperglycemic drugs metformin, thiazolidinediones [TZD], α-glucosidase inhibitors, glucagon-like peptide 1 agonists, basal insulin has delayed or even prevented the development of diabetes.

This is a misinterpretation of the situation. These drugs have simply treated a level of glycemia lower than the diagnostic criteria for diabetes retarding its increase to the level at which a diagnosis of diabetes would occur.

After these drugs were discontinued, the prevalence of diabetes in treated individuals mirrored that in the placebo group. However, the time course of action of a drug is much more related to its tissue biologic effects than to the pharmacokinetics of its concentration in the blood.

It is well established that it takes 2—4 weeks for both metformin and sulfonylureas to exert their maximal effects when started 33 — Although the author could find no studies examining the time course of the effect of metformin wearing off, it takes 2—4 weeks for the effect of a sulfonylurea tolazamide to completely dissipate Troglitazone, a TZD that was removed from the market because of hepatic toxicity, was used for a mean of 0.

In those who had not developed diabetes during the intervention period, the rate of development of diabetes was the same in both groups during the 2- to 3-month washout period after both rosiglitazone and its placebo were discontinued 39 and 1.

The Outcome Reduction With Initial Glargine Intervention ORIGIN study compared people with CVD risk factors who also had IFG, IGT, or early type 2 diabetes and who were given either glargine insulin or placebo The pathophysiologic abnormalities of insulin resistance and progressive β-cell dysfunction that characterize prediabetes were not fundamentally altered by these drug treatments 42 , 43 , which explains the lack of any long-term effects when these medications were discontinued Even so, should metformin treatment be offered to individuals whose glycemic parameters are near the diagnosis for diabetes, i.

There are three arguments against this. Second, approximately one-third of people with prediabetes return to normal glucose regulation NGR. After the study ended, the percent of participants who returned to NGR 1. Third, as described previously, the diagnostic criteria for diabetes were selected because the risk for microvascular complications increased beyond that level of glycemia.

Metformin, the preferred initial drug for treating patients with diabetes, is started to lower glycemia to levels that are not associated with this risk. Five studies 51 — 55 have shown that the development or progression of retinopathy and microalbuminuria over a 6- to year period was almost nil if A1C levels were kept below 7.

So, given that two-thirds of people with prediabetes do not develop diabetes over many years 45 — 47 , and in approximately one-third glycemia returns to normal 40 , 45 , 47 — 50 , why put people who are not at risk for the microvascular complications of diabetes when prediabetes is diagnosed on a drug possibly for the rest of their lives that has no immediate advantage except to lower subdiabetes glycemia to even lower levels?

This Perspective is not arguing against the benefit of delaying the development of diabetes. Rather, it is pointing out that the benefit of delay achieved with medication must be weighed against the potential adverse effects of the drug, its cost, and the important fact that a large number of people with the diagnosis of prediabetes will not develop diabetes and metformin would be of no benefit for them.

The argument is that lifestyle interventions, especially weight loss in overweight and obese individuals, should be pursued rather than use of a medication.

It seems more prudent to identify individuals at the highest risk for developing diabetes—i. Meanwhile, these individuals should be intensely counseled on lifestyle interventions to reduce the risk of developing diabetes, and the risk factors for CVD should be aggressively addressed.

See accompanying article, p. Duality of Interest. No conflicts of interest relevant to this article were reported. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care.

Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 43, Issue 9. Next Article. Article Information. Article Navigation. Perspectives in Care August 11 Metformin Should Not Be Used to Treat Prediabetes Mayer B.

Davidson Charles R. Drew University, Los Angeles, CA. Corresponding author: Mayer B. Davidson, mayerdavidson cdrewu. This Site. Google Scholar. Diabetes Care ;43 9 — Article history Received:. Connected Content. A commentary has been published: Metformin Should Be Used to Treat Prediabetes in Selected Individuals.

Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.

Diabetes Prevention Program Research Group. Long-term effects of metformin on diabetes prevention: identification of subgroups that benefited most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Search ADS. More evidence for a prevention-related indication for metformin: let the arguments resume!

Centers for Disease Control and Prevention. National Diabetes Statistics Report, Department of Health and Human Services. Accessed 2 February National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance.

Clinical irrelevance of the current diagnostic criteria for abnormal carbohydrate metabolism in asymptomatic individuals. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.