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". In this phase insulin doses become very small, and insulin treatment can sometimes even be interrupted for a while [1].

Over time, as the remaining beta cells are destroyed by the autoimmune process, your requirements gradually rise. They 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;
• 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. You follow the trends every day and apply the small adjustments agreed in advance. Larger changes to the regimen and unclear situations — repeated hypoglycemia, high blood glucose for several days in a row, an acute illness — are discussed with your doctor. The adjustment remains something carried out together with your medical team [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 hypoglycemia 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". Here 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 hypoglycemia [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 hyperglycemia, possibly with ketone bodies (acidic substances the body makes when it does not have enough insulin and burns fat instead of glucose), 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, as the figure below shows:

• partial remission, or the "honeymoon" — often follows immediately after diagnosis, characterized by a reduced or sometimes even absent need for external insulin;
• the intensification phase — the remaining beta cells gradually disappear, doses rise and treatment regimens become more complex, with frequent adjustments;
• the long-standing diabetes phase — one's own insulin production is almost absent and attention gradually shifts towards preventing and detecting chronic complications;
• the stage of chronic complications that have already appeared (for example chronic kidney disease) — attention now turns to slowing their progression, for example to postpone the need for dialysis.

These stages do not have rigid boundaries and do not progress in the same way in every patient. 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. Episodes of severe hypoglycemia and of ketoacidosis are frequent and interfere significantly with daily life, school, work and relationships. The causes are usually multiple and include:

• impaired hormonal counterregulation;
• impaired awareness of hypoglycemia;
• gastroparesis that delays the absorption of food;
• intestinal malabsorption (for example untreated celiac disease);
• eating disorders;
• depression;
• severe anxiety;
• psychosocial difficulties;
• systematic errors in insulin administration.

More rarely it is a matter of unusual insulin resistance [6]. If thoughts of self-harm appear, ask for help the same day; the situations that call for emergency care are listed in the medical disclaimer.

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 glycemic variability and the frequency of severe hypoglycemia [7]. Beyond technology, what also matters is training in recognizing hypoglycemia, carefully adjusting glycemic targets and assessing associated digestive diseases. Hypoglycemia means a blood glucose below 70 mg/dL (3.9 mmol/L): you take 15 g of fast-acting carbohydrate and recheck after 15 minutes. The complete steps are on the pages about what hypoglycemia is and about how to treat it. Equally important are specialist psychological support, treating eating disorders and sometimes simplified treatment 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 type 1 diabetes do not appear overnight. They generally develop over several years and depend strongly on glycemic control, blood pressure, lipid profile and 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. It should not, however, begin before the age of 11 or before puberty starts, whichever comes first [8]. By comparison, in type 2 diabetes the eye examination is performed right from the time of diagnosis, regardless of age. 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. They mean that in this time any changes are usually very small and reversible if you act promptly. Glycemic 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, so you reduce the risk that vision loss, kidney failure or cardiovascular events appear, although you do not remove it completely [9].

The most important factor influencing the course of type 1 diabetes is long-term glycemic control, expressed through time in range (TIR), glycemic variability and HbA1c. Persistently high HbA1c values, above 8% (64 mmol/mol), and large swings between hypo- and hyperglycemia 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 celiac disease, autoimmune thyroiditis or other autoimmune conditions, can also worsen the course when undiagnosed and untreated, through malabsorption, unpredictable hypoglycemia or hormonal imbalances.

Equally important are the behavioral and psychosocial factors, which are often underestimated. Poor adherence to insulin therapy and to self-monitoring of blood glucose significantly increases the long-term risk of chronic complications. So do missed periodic check-ups for detecting complications, a lack of ongoing therapeutic education and difficulties in accessing modern technology. Depression, anxiety and eating disorders also weigh heavily, as does "diabetes distress", the exhaustion caused by the daily management of the disease. All of these 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 also 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. Insulin is stopped only if the medical team decides so, under clear conditions of safety; otherwise the treatment is continued even when the doses seem very small. Keeping up the injections partly protects residual beta function and prevents an 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, lowers 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 between meals. In some women, the first trimester of pregnancy brings increased insulin sensitivity, but this is not real relief: the risk of hypoglycemia rises, so the doses are reviewed together with the medical team and blood glucose is monitored more often, including at night. These periods do not mean that the disease has disappeared. With the right combination of treatment, behavioral changes and the adoption of modern technologies, type 1 diabetes simply becomes 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 behaviors (skipping injections, alcohol use, eating disorders). Diabetes care must here 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 glycemic targets in frail patients, those with multiple comorbidities or with limited life expectancy. Here the risk of hypoglycemia 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 is to avoid hypoglycemia, 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. Decisions are made together with you, taking into account your real values, goals and possibilities [2].