By prevention we mean the effort made to forestall and avert certain negative or undesirable states, actions or consequences. In this case, prevention in type 1 and type 2 diabetes mellitus means forestalling, or even averting, the full clinical onset of these diseases.
Recent epidemiological data suggest that diabetes mellitus is tending to take on epidemic proportions. In 2024, 589 million people worldwide are living with type 2 diabetes mellitus, and that number is set to rise to 852.5 million by 2050, an increase of some 45%. At the same time, 635 million people have impaired glucose tolerance (prediabetes), raising their risk of developing type 2 diabetes. In effect 1 in 9 people has diabetes, and of those affected, one in two does not know they have it (1).
As regards type 1 diabetes, in 2024, 9.15 million people are affected (1). 503,000 new cases of T1DM appeared across all ages in 2024, with 219,000 occurring in children and adults under 20 years of age (2). The incidence in Greece is 9 per 100,000 in Athens and considerably lower in rural and semi-urban areas, with the rate in Crete reaching 4.6 per 100,000 (3). Given the large increase observed worldwide, the question reasonably arises: are we in fact able to prevent the progression of either type 1 or type 2 diabetes mellitus?
Type 1 diabetes mellitus (T1DM), or insulin-dependent diabetes, arises from autoimmune destruction of the pancreatic beta cells, resulting in complete insulin deficiency. This process appears to be triggered by the interaction between environmental and genetic factors. Before the clinical onset of T1DM there is a pathogenic process that develops progressively. Essentially, the risk of developing T1DM is greater in genetically predisposed individuals.
Initially both the mass and the function of the pancreatic beta cells are normal. With the appearance of an environmental stimulus, of as yet unknown cause, the inflammatory process begins, during which inflammatory cells infiltrate the endocrine portion of the pancreas. At this stage the destruction of the beta cells begins with the development of autoantibodies, which in effect lead to the destruction of our own cells. So at this first stage we have positive autoantibodies and normal blood glucose values.
Destruction of the beta cells then follows progressively, with impaired insulin secretion. At this point the process of progressive destruction is either reversed, with progressive improvement in beta-cell function, or it leads to the complete destruction of the cell with total absence of insulin secretion. At this second stage prediabetes may appear, with HbA1c values of 5.7-6.4% or a rise of ≥10% compared with a previous measurement. At the third and final stage the patient becomes symptomatic because of high blood glucose values, and the diagnosis of T1DM is made (4,7).
Given the pathophysiological process described above, are we able to halt the onset of T1DM at any of the stages we have just seen?
On 17 November 2022, for the first time, the United States Food and Drug Administration (FDA) approved the administration of the monoclonal antibody (anti-CD3) known as teplizumab, or Tzield, for the prevention of T1DM in people aged 8 years and over who are at stage 1b T1DM, have not developed diabetes, but are at high risk of developing it. The drug is given intravenously daily for 14 days and appears to delay the onset of diabetes by 3 years. The main adverse effects of the drug are usually transient, the most frequent being leukopenia, rash and headache. In addition there are warnings regarding symptoms of cytokine release syndrome, the risk of developing serious infections, lymphopenia and hypersensitivity reactions, along with the recommendation that all age-appropriate vaccinations be completed before the drug is given.
Turning to type 2 diabetes mellitus (T2DM), which accounts for the greatest proportion of people with diabetes, the picture appears to change and we are in a position to halt its course.
First of all, we need to identify who is at increased risk of developing T2DM.
People who are overweight or obese (BMI ≥25) and who have one or more risk factors, such as:
- Prediabetes or HbA1c ≥5.7%
- Family history of diabetes mellitus
- Gestational diabetes
- Hypertension (≥140/90) or on medication
- HDL cholesterol <40 mg/dl in men or <50 mg/dl in women
- Triglycerides >150 mg/dl
- History of cardiovascular disease
- Lack of physical activity
- Women with a history of polycystic ovaries
- Clinical conditions with insulin resistance present (obesity, acanthosis nigricans and others)
- Treatment with corticosteroids, thiazide diuretics and antipsychotic medicines
If a person meets the above criteria, at what age should screening begin, and how often should it be repeated if it is negative?
Screening usually begins after the age of 45. However, it may begin at any age if the person is overweight or obese and has one or more risk factors for developing T2DM.
That person then undergoes a glucose curve with 75 g of glucose. If it is normal, screening is repeated every 3 years; whereas if it is abnormal and indicates prediabetes [impaired fasting glucose (fasting glucose 100-125 mg according to the American Diabetes Association, or 110-125 mg according to the Hellenic Diabetes Association) or impaired glucose tolerance (a 2-hour glucose value on the glucose curve between 140-199 mg)], or both, screening is repeated annually.
Which people should take preventive measures in order to avoid the risk of progressing to T2DM?
People with prediabetes (impaired fasting glucose or impaired glucose tolerance), or both, and HbA1c values of 5.7-6.4%. In addition, people who are overweight or obese, and people with a positive family history (6).
If a person is overweight or obese and one or both parents have diabetes mellitus, what should they do?
They should immediately undergo a glucose curve with 75 g of glucose. In the days before the test they should not undertake any form of fasting. On the day of the test they will be fasting and, if they smoke, must not have smoked beforehand. In addition, they should remain seated throughout the test, because the slightest exertion — even walking — can lead to erroneous results.
Beyond heredity, which people should exercise greater caution because of an increased risk of developing type 2 diabetes mellitus?
People who meet the criteria for what is called the metabolic syndrome, because people with metabolic syndrome have a several-fold higher risk both of developing type 2 diabetes mellitus and of cardiovascular disease. A person is defined as having metabolic syndrome if they meet 3 of the following 5 components:
- Increased waist circumference: >102 cm in men or 88 cm in women (today the thresholds have been narrowed further still, to 94 cm in men and 80 cm in women).
- Raised blood pressure: >130/85 mmHg, or taking antihypertensive treatment.
- Impaired fasting glucose (>100 mg/dl) or impaired glucose tolerance.
- Raised triglyceride value >150 mg/dl.
- Low HDL value (<40 mg/dl in men and <50 mg/dl in women).
People with metabolic syndrome should therefore immediately undergo a glucose curve with 75 g of glucose, in order to establish precisely whether they have any disturbance of blood glucose. Beyond that, they should immediately address all the components of the metabolic syndrome, through weight loss as well as control of blood pressure and of the lipid profile.
What is the most powerful means of preventing the onset of T2DM in people with prediabetes?
Strict lifestyle and dietary intervention, which divides into two pillars: on the one hand correct nutrition, aimed at reducing and maintaining body weight at least 5-7% below its previous level; and on the other physical exercise, comprising 30 minutes of, for example, brisk walking, 5 times a week. Prevention lies in changing behaviour and adopting the lifestyle and dietary interventions described above.
In doing so, studies have shown a 58% reduction in the likelihood of progression to T2DM within three years. In the European Diabetes Prevention Study (EDIPS), maintaining a 5% weight loss over three years reduced the risk of developing T2DM by 89%. Three of the largest lifestyle-intervention studies conducted for the prevention of T2DM showed that, beyond everything else, the effect was also long-lasting, since the reduction in progression to T2DM persisted over the years: a 43% reduction at 20 years in the Da Qing study, a 43% reduction at 7 years in the Finnish Diabetes Prevention Study (DPS), and a 34% reduction at 10 years and 27% reduction at 15 years in the U.S. Diabetes Prevention Program Outcomes Study (DPPOS) (6,7,8).
What changes should we make to our body weight and our diet in order to prevent T2DM?
Gradual weight loss is recommended, aiming at a reduction of around 0.5-1 kg per week. The loss of one kilogram is associated with a 16% reduction in relative risk, and a 10% loss of body weight is enough to reduce the future risk of developing T2DM by 80%. The daily calories needed to maintain body weight should be calculated, and 500-1000 calories per day subtracted (depending on the starting body weight).
Diets high in fat, of high glycaemic index and low in fibre are associated with an increased risk of diabetes. A primary goal is to reduce daily fat intake to below 30% of daily energy intake, and in particular to reduce saturated fatty acids (such as trans fats, for example butter and mayonnaise) to below 10% of daily intake. On the other hand, the consumption of monounsaturated fatty acids, such as olive oil, is recommended.
Adopting the Mediterranean dietary pattern (rich in fruit, vegetables, olive oil, fish and lean meat), and in particular fibre intake (25-30 g per day), favours the prevention of T2DM. The PREDIMED study showed that a Mediterranean diet with added extra virgin olive oil leads to a 40% reduction in the appearance of diabetes, while a Mediterranean diet with added nuts leads to a reduction of 18%. Higher intake of nuts, berries, yoghurt, coffee and tea appears from studies to be associated with a lower risk of developing T2DM. On the other hand, the consumption of red and processed meat, of fried foods and particularly potatoes, and of sugar-sweetened soft drinks or processed carbohydrates, increases the risk of its appearance.
Certain vitamins and trace elements are associated with a lower risk of developing diabetes. High magnesium intake reduces the risk, whereas the consumption of chromium and zinc has no clear effect. The relationship between 25-hydroxyvitamin D and the incidence of diabetes is disputed; we need further studies to clarify the relationship between the two. Alcohol consumption shows a U-shaped relationship with the appearance of T2DM: both low and high quantities are associated with a higher risk of developing T2DM (7,8).
What is the effect of exercise on the prevention of type 2 diabetes mellitus (T2DM)?
A recent study showed that a sedentary life increases the risk of developing T2DM. On the other hand, studies characteristically report that increased physical activity and exercise are associated with a 25-40% reduction in the relative risk of developing T2DM. It appears that even in the absence of weight loss, increased physical activity and exercise reduce the incidence of T2DM, although it is indisputable that those who move more tend to lose more body weight. As regards exercise, the guidelines recommend 30 minutes daily or 150 minutes weekly of moderate or vigorous exercise, including brisk walking, resistance exercises, gardening or other activities of increased physical activity (8).
Can pharmacological agents be used in people with prediabetes in order to prevent the onset of diabetes?
The answer is yes. Medicines such as metformin, alpha-glucosidase inhibitors, orlistat, GLP-1 agonists and thiazolidinediones have been shown to reduce the appearance of diabetes to varying degrees in people with prediabetes. Of these, metformin has the strongest proven indication and is the safest for the prevention of diabetes. As for the remaining agents, they are not used, as much because of cost as because of the adverse effects they present. Although metformin was less effective than lifestyle and dietary intervention for the prevention of T2DM, it appears to be of benefit within the first 10 years: it reduces by 30% the likelihood of a person with prediabetes progressing to diabetes, against the 58% reduction produced by lifestyle and dietary intervention, as we saw above (7).
Which people may benefit from the preventive use of metformin?
People with prediabetes and a BMI ≥35 kg/m², aged under 60; women with gestational diabetes; and people who are under lifestyle and dietary intervention but whose glycated haemoglobin is nonetheless rising. In the DPP study, in women with gestational diabetes, giving metformin in combination with lifestyle and dietary intervention led to a 50% reduction in the development of T2DM, and both of these interventions remained effective over 10 years of follow-up (7).
As is well known, people with prediabetes, beyond the risk of developing type 2 diabetes mellitus, also carry an increased risk of cardiovascular disease.
Which are the risk factors they should pay attention to, beyond the disturbance of blood glucose?
Particular emphasis should be placed on reducing body weight in people who are overweight or obese, and especially on reducing central obesity (waist circumference >94 cm in men and 80 cm in women). Blood pressure should be monitored and controlled with whatever medication each person is taking. Finally, emphasis should be placed on control of the lipid profile — reducing triglycerides below 150 mg/dl, raising HDL above 40 mg/dl in men and 50 mg/dl in women, and reducing LDL below the thresholds your treating doctor will indicate to you, taking into account the other risk factors you may have. It would be an omission not to mention stopping smoking as well, since it has been shown to worsen the atherosclerotic process significantly.
References
- IDF Atlas, 11th edition 2025.
- Kasper et al. (2005). Harrison's Principles of Internal Medicine (16th ed.). New York: McGraw-Hill.
- Bartsokas et al. Epidemiology of childhood IDDM in Athens. Trends in incidence for the years 1989-1995. Diabetologia 1998; 41:245-248.
- Palmer JP. Prediction, Prevention and Genetic Counseling in IDDM. John Wiley and Sons, England Ltd. 1995: 255-390.
- Paschou P. Prevention of Type 1 Diabetes Mellitus. Archives of Hellenic Medicine 2001; 18(6):566-574.
- Clinical practice guidelines 2018 — Hellenic Diabetes Association.
- Standards of Medical Care 2018, ADA guidelines.
- Evidence-based nutrition guidelines for the prevention and management of Diabetes. March 2018. Diabetes UK 2018 nutrition working group.