📘 Long-term evolution of type 1 diabetes

At the moment of diagnosis, insulin requirements are often higher because very high blood glucose values produce a phenomenon called glucotoxicity. This temporarily reduces the body's sensitivity to insulin and thus blocks part of what remains of beta cell function. After a few days or, more rarely, weeks of correct treatment, blood glucose stabilizes at lower levels, glucotoxicity disappears and consequently insulin requirements decrease significantly. Many patients with diabetes then go through a period of partial remission, popularly known as the "honeymoon", when insulin doses become very small, and sometimes insulin treatment can even be temporarily interrupted [1].

Over time, as the remaining beta cells are destroyed by the autoimmune process, your requirements gradually increase and stabilize at the typical values of an adult with T1D, around 0.5–1.0 units per kilogram of body weight per day, divided between basal and prandial insulin. This number, however, is not fixed for life. Increases in insulin requirements can be induced by puberty (growth and sex hormones), pregnancy, decrease of muscle mass, weight gain, sedentary lifestyle, infections, corticotherapy or the appearance of major stress. Conversely, regular physical activity, weight loss and a balanced diet can reduce your insulin doses. That is why insulin dose adjustment is in fact a continuous process, done together with the medical team, but especially by you [2].

Insulin sensitivity is not constant throughout life, but changes depending on age, hormones, body weight and level of physical activity. In young children, insulin sensitivity is usually very high, which is why doses are small and the risk of hypoglycemia is increased. During puberty a physiological insulin resistance appears, generated by growth hormone and sex hormones, and doses increase significantly, sometimes even doubling. In young adults, insulin sensitivity increases compared to puberty, stabilizes, but remains influenced by the level of movement, sleep, stress and the menstrual cycle in women [3].

If over time you accumulate extra kilograms or become sedentary, you can end up in a situation popularly called "double diabetes", in which on top of T1D an insulin resistance similar to that of T2D is superimposed, and insulin requirements can increase very much. Regular physical activity, especially the combination of aerobic and strength exercises, increases your insulin sensitivity and can reduce doses. In the elderly, insulin sensitivity varies a bit more. On the one hand, the decrease of muscle mass (sarcopenia) induces insulin resistance, and on the other hand the decrease of food intake and of renal function prolongs insulin's effect and increases the risk of hypoglycemia [3].

Yes, type 1 diabetes has three official stages, and in the long term, after the appearance of stage 3, several practical phases of evolution can be described. In stage 1 of T1D you already have specific autoantibodies (at least two positive), but blood glucose is still normal. In stage 2 you have autoantibodies and prediabetes, that is, slightly elevated blood glucose values, without obvious symptoms. Stage 3 corresponds to clinically manifest diabetes, with symptomatic hyperglycemia, possibly with ketone bodies, the moment when the patient is diagnosed and insulin therapy begins [4].

After the onset of stage 3 of T1D, evolution continues in several practical phases. Immediately after diagnosis, partial remission or the "honeymoon" often follows, characterized by reduced or sometimes even absent need for external insulin. Then comes the intensification phase, in which the remaining beta cells gradually disappear, doses increase and therapeutic regimens become more complex, with frequent adjustments. Finally comes the long-duration diabetes phase, in which one's own insulin production is almost absent, and attention gradually shifts toward preventing and detecting chronic complications. Another stage is the one in which chronic complications have already appeared (e.g., chronic kidney disease) and attention now turns to preventing the complications of these chronic complications (e.g., dialysis). These stages do not have rigid borders and do not progress the same way in all patients, but understanding them helps you anticipate the changes that may follow and discuss more clearly with your medical team [5].

The term "brittle diabetes", also known as "unstable diabetes", describes a form in which blood glucose values vary unpredictably and very widely, with frequent episodes of both severe hypoglycemia and ketoacidosis, which significantly interfere with daily life, school, work and relationships. Causes are usually multiple and include impaired hormonal counterregulation, lack of hypoglycemia awareness, gastroparesis that delays food absorption, intestinal malabsorption (for example untreated celiac disease), eating disorders, depression, severe anxiety, psychosocial difficulties or systematic errors in insulin administration. More rarely it is a matter of unusual insulin resistance [6].

Today, "brittle diabetes" is much less frequent compared to previous decades, because modern technology has radically changed the care of T1D. Continuous glucose monitoring, insulin pumps and especially automated insulin delivery systems significantly reduce glycemic variability and the frequency of severe hypoglycemia [7]. Beyond technology, what also matters is patient re-education in recognizing hypoglycemia, careful adjustment of glycemic targets, evaluation of associated digestive diseases, specialized psychological support, treatment of eating disorders and sometimes simplified therapeutic regimens. If you recognize yourself in this picture, it is essential not to blame yourself. Glycemic instability almost always has identifiable and treatable causes, and a skilled multidisciplinary team can help you regain control [6].

Chronic complications of T1D do not appear overnight; they develop in general over the course of several years and depend strongly on glycemic control, blood pressure, lipid profile and the presence of other risk factors, such as smoking. Screening for retinopathy through ophthalmologic examination with pupil dilation is recommended at five years from onset in adults with T1D. In children and adolescents with T1D, the initial screening is recommended after 3–5 years of disease evolution, but not earlier than the age of 11 or the onset of puberty, depending on which appears first [8]. As a side note, for patients with T2D, regardless of age, the ophthalmologic examination is performed at the moment of diagnosis. For diabetic kidney disease, urinary albumin and serum creatinine measurement with estimation of the glomerular filtration rate begin at five years from onset. Screening for diabetic peripheral neuropathy in adults with T1D is initiated at five years from diagnosis and is repeated at least annually. In children and adolescents, the annual foot examination is performed after five years of disease evolution, starting with puberty or the age of 11 [9].

These intervals do not mean that you have a guarantee of a five-year "free" period, but only that during this period any possible changes are usually very small and reversible if action is taken in time. Glycemic control close to the target, with HbA1c below 7% (53 mmol/mol) in the majority of adults, significantly delays the appearance of chronic complications and reduces their severity. Early screening is useful precisely because it allows the detection of minimal, asymptomatic lesions, when treatment is most effective. Early retinopathy, mildly elevated albuminuria or moderate dyslipidemia can be controlled with simple interventions, before vision loss, kidney failure or cardiovascular events become a real risk [9].

The most important factor that influences the evolution of T1D is long-term glycemic control, expressed through time spent in target (TIR), glycemic variability and HbA1c. Constantly elevated HbA1c values, above 8% (64 mmol/mol), and large oscillations between hypo- and hyperglycemia increase the risk of microvascular complications (eyes, kidneys, nerves) and macrovascular complications (heart, brain, peripheral vessels) [11]. To these are added the classic cardiovascular risk factors: arterial hypertension, dyslipidemia, smoking, obesity, sedentary lifestyle and unbalanced diet [10]. Associated diseases, such as celiac disease, autoimmune thyroiditis or other autoimmune diseases, when undiagnosed and untreated can also worsen the evolution through malabsorption, unpredictable hypoglycemia or hormonal imbalances.

Equally important are the behavioral and psychosocial factors, which are often underestimated. Low adherence to insulin therapy and self-monitoring of blood glucose, omission of periodic check-ups for detecting complications, lack of continuous therapeutic education and difficulties in accessing modern technology significantly increase the risk of chronic complications in the long term. Depression, anxiety, eating disorders and the phenomenon of "diabetes distress" (the exhaustion caused by daily disease management) reduce your capacity to take care of yourself in general, not only related to diabetes. That is why a good evolution means more than correct doses of insulin and presupposes regular check-ups, screening for complications performed in time, psychological support when needed and a medical team you can rely on in the long term [11].

Yes, the best-known period of "relief" is partial remission, popularly called the "honeymoon", which appears in many patients with type 1 diabetes in the first weeks after starting insulin therapy. In this phase, the remaining beta cells partially recover their function once glucotoxicity is removed, and your endocrine pancreas seems to be recovering. Insulin requirements drop below 0.5 units per kilogram of body weight per day, blood glucose values are nearly normal, and HbA1c drops below 7% (53 mmol/mol) with small doses of insulin. This period can last from a few weeks to a few months, occasionally even a few years, but it is temporary because the autoimmune process continues to destroy beta cells. If it cannot be stopped under clear safety conditions, insulin must be continued even when doses seem very small, because maintaining the injections partially protects residual beta function and prevents abrupt relapse into hyperglycemia or ketoacidosis [12].

There are also other moments when diabetes can seem "easier" to manage. The introduction of modern technology, such as continuous glucose monitoring and automated insulin delivery systems, reduces glycemic variability, decreases the frequency of hypoglycemia and frees up your mental attention [13]. A regular routine of physical exercise increases your insulin sensitivity and stabilizes blood glucose values between meals. In some women, the first trimester of pregnancy brings increased insulin sensitivity and sometimes somewhat more mild hypoglycemia, but evolution is variable and requires careful monitoring. These periods do not mean that the disease has disappeared, only that, using the right combination of treatment, behavioral changes and the adoption of modern technologies, type 1 diabetes can become more predictable and less invasive in your daily life.

Care of T1D must be adapted to the stage of life you are in, because priorities, risks and objectives differ. In young children and school-age children, the emphasis is on family, on harmonious growth, on safety in kindergarten and school and on educating the parents. In adolescence, challenges related to the desire for autonomy, peer pressure, risk behaviors (omitting injections, alcohol consumption, eating disorders) appear, and the approach to diabetes care must also include planning the transition to adult services. In young adults, the emphasis shifts to education, career, relationships, contraception and pregnancy planning, to consolidating therapeutic independence and to optimal use of technology. In middle-aged adults, balance between work and personal life, intensification of screening for chronic complications and aggressive control of cardiovascular risk factors become essential [8].

In the elderly, the approach changes significantly, with more relaxed glycemic targets in fragile patients, with multiple comorbidities or with limited life expectancy, because the risk of hypoglycemia exceeds the benefit of very strict control. HbA1c can be accepted up to 8–8.5% (64–69 mmol/mol) in the fragile, the priority being avoiding hypoglycemia, preventing falls, simplifying therapeutic regimens and careful management of the number of recommended medications. Cognitive decline, decreased visual acuity, tremor and arthrosis can make insulin administration difficult, and the involvement of the family or caregivers becomes again very important. Regardless of age, the common principle is that treatment must be adapted to the person, not the other way around, and decisions are made together with you, taking into account your real values, objectives and possibilities [2].