The long-term course of type 1 diabetes

At 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 so blocks part of what remains of beta cell function. After a few days or, more rarely, weeks of proper treatment, blood glucose settles at lower levels, glucotoxicity resolves and, as a result, insulin requirements fall 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 interrupted temporarily [1].

Over time, as the remaining beta cells are destroyed by the autoimmune process, your requirements gradually rise and settle at the values typical of an adult with type 1 diabetes, around 0.5–1.0 units per kilogram of body weight per day, split between basal and mealtime insulin. This figure, however, is not fixed for life. Increases in insulin requirements can be triggered by puberty (growth and sex hormones), pregnancy, loss of muscle mass, weight gain, a sedentary lifestyle, infections, corticosteroid treatment or major stress. Conversely, regular physical activity, weight loss and a balanced diet can reduce your insulin doses. That is why adjusting insulin doses is in fact a continuous process, carried out together with your medical team, but above all by you [2].

Insulin sensitivity is not constant throughout life; it changes with 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 hypoglycaemia is increased. During puberty a physiological insulin resistance appears, driven by growth hormone and sex hormones, and doses rise significantly, sometimes even doubling. In young adults, insulin sensitivity increases compared with puberty and settles, but it remains influenced by the amount of physical activity, sleep, stress and, in women, the menstrual cycle [3].

If over time you gain extra weight or become sedentary, you can end up in a situation popularly called “double diabetes”, in which an insulin resistance similar to that of type 2 diabetes is superimposed on type 1 diabetes, and insulin requirements can rise considerably. Regular physical activity, especially the combination of aerobic and strength exercise, increases your insulin sensitivity and can reduce doses. In older people, insulin sensitivity varies somewhat more. On the one hand, loss of muscle mass (sarcopenia) causes insulin resistance; on the other hand, reduced food intake and declining kidney function prolong insulin's effect and increase the risk of hypoglycaemia [3].

Yes, type 1 diabetes has three official stages, and over the long term, after stage 3 has appeared, several phases of evolution can be described. In stage 1 of type 1 diabetes 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 raised blood glucose values without obvious symptoms. Stage 3 corresponds to clinically manifest diabetes, with symptomatic hyperglycaemia, possibly with ketone bodies, the point at which the patient is diagnosed and insulin therapy begins [4].

After the onset of stage 3 of type 1 diabetes, the course continues through several practical phases. Immediately after diagnosis there is often partial remission, or the “honeymoon”, characterised by a reduced or sometimes even absent need for external insulin. Then comes the intensification phase, in which the remaining beta cells gradually disappear, doses rise and treatment regimens become more complex, with frequent adjustments. Finally comes the long-standing diabetes phase, in which one's own insulin production is almost absent and attention gradually shifts towards preventing and detecting chronic complications. Another stage is the one in which chronic complications have already appeared (for example chronic kidney disease) and attention now turns to preventing the complications of those chronic complications (for example dialysis). These stages do not have rigid boundaries and do not progress in the same way in every patient, but understanding them helps you anticipate the changes that may follow and talk more clearly with your medical team [5].

The term “brittle diabetes”, also known as “unstable diabetes”, describes a form in which blood glucose varies unpredictably and very widely, with frequent episodes of both severe hypoglycaemia and ketoacidosis that interfere significantly with daily life, school, work and relationships. The causes are usually multiple and include impaired hormonal counterregulation, impaired awareness of hypoglycaemia, gastroparesis that delays the absorption of food, intestinal malabsorption (for example untreated coeliac 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 far less common than in previous decades, because modern technology has radically changed the care of type 1 diabetes. Continuous glucose monitoring, insulin pumps and, above all, automated insulin delivery systems significantly reduce glycaemic variability and the frequency of severe hypoglycaemia [7]. Beyond technology, what also matters is re-educating the patient in recognising hypoglycaemia, carefully adjusting glycaemic targets, assessing associated digestive diseases, providing specialist psychological support, treating eating disorders and sometimes using simplified treatment regimens. If you recognise yourself in this picture, it is essential not to blame yourself. Glycaemic instability almost always has identifiable and treatable causes, and a skilled multidisciplinary team can help you regain control [6].

Chronic complications of type 1 diabetes do not appear overnight; they generally develop over the course of several years and depend strongly on glycaemic control, blood pressure, lipid profile and the presence of other risk factors, such as smoking. Screening for retinopathy through an eye examination with pupil dilation is recommended five years after onset in adults with type 1 diabetes. In children and adolescents with type 1 diabetes, the initial screening is recommended after 3–5 years of disease, but not before the age of 11 or the onset of puberty, whichever comes first [8]. As a side note, for patients with type 2 diabetes, regardless of age, the eye examination is performed at the time of diagnosis. For diabetic kidney disease, measurement of urinary albumin and serum creatinine with estimation of the glomerular filtration rate begins five years after onset. Screening for diabetic peripheral neuropathy in adults with type 1 diabetes begins five years after diagnosis and is repeated at least yearly. In children and adolescents, the annual foot examination is performed after five years of disease, starting from puberty or the age of 11 [9].

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

The most important factor influencing the course of type 1 diabetes is long-term glycaemic control, expressed through time in range (TIR), glycaemic variability and HbA1c. Persistently high HbA1c values, above 8% (64 mmol/mol), and large swings between hypo- and hyperglycaemia increase the risk of microvascular complications (eyes, kidneys, nerves) and macrovascular complications (heart, brain, peripheral vessels) [10]. To these are added the classic cardiovascular risk factors: arterial hypertension, dyslipidaemia, smoking, obesity, a sedentary lifestyle and an unbalanced diet [11]. Associated diseases, such as coeliac disease, autoimmune thyroiditis or other autoimmune conditions, can also worsen the course when undiagnosed and untreated, through malabsorption, unpredictable hypoglycaemia or hormonal imbalances.

Equally important are the behavioural and psychosocial factors, which are often underestimated. Poor adherence to insulin therapy and self-monitoring of blood glucose, missing the periodic check-ups for detecting complications, lack of ongoing therapeutic education and difficulties in accessing modern technology significantly increase the risk of chronic complications over the long term. Depression, anxiety, eating disorders and the phenomenon of “diabetes distress” (the exhaustion caused by the daily management of the disease) reduce your capacity to look after yourself in general, not only in relation to diabetes. That is why a good course means more than correct insulin doses; it involves regular check-ups, timely screening for complications, psychological support when needed and a medical team you can rely on over the long term [10].

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 partly recover their function once glucotoxicity is removed, and your endocrine pancreas seems to be recovering. Insulin requirements fall below 0.5 units per kilogram of body weight per day, blood glucose is 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 conditions of safety, insulin must be continued even when the doses seem very small, because keeping up the injections partly protects residual beta function and prevents an abrupt relapse into hyperglycaemia 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 glycaemic variability, lowers the frequency of hypoglycaemia and frees up your mental attention [13]. A regular routine of physical exercise increases your insulin sensitivity and stabilises blood glucose between meals. In some women, the first trimester of pregnancy brings increased insulin sensitivity and sometimes somewhat more frequent mild hypoglycaemia, but the course is variable and requires careful monitoring. These periods do not mean that the disease has disappeared, only that, using the right combination of treatment, behavioural changes and the adoption of modern technologies, type 1 diabetes can become more predictable and less intrusive in your daily life.

Care of type 1 diabetes must be adapted to the stage of life you are in, because the priorities, risks and goals differ. In young children and school-age children, the emphasis is on the family, on healthy growth, on safety at nursery and school and on educating the parents. In adolescence, challenges arise related to the desire for autonomy, peer pressure and risk behaviours (skipping injections, alcohol use, eating disorders), 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 making optimal use of technology. In middle-aged adults, the balance between work and personal life, the intensification of screening for chronic complications and the aggressive control of cardiovascular risk factors become essential [8].

In older people, the approach changes significantly, with more relaxed glycaemic targets in frail patients, those with multiple comorbidities or with limited life expectancy, because the risk of hypoglycaemia outweighs the benefit of very tight control. HbA1c can be accepted up to 8–8.5% (64–69 mmol/mol) in the frail, the priority being to avoid hypoglycaemia, prevent falls, simplify treatment regimens and carefully manage the number of medications prescribed. Cognitive decline, reduced visual acuity, tremor and arthritis can make insulin administration difficult, and the involvement of the family or carers becomes very important once again. Whatever the 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, goals and possibilities [2].