Diabetes is a chronic disease in which there is an increase in blood sugar, or blood sugar levels, which the body is unable to bring back to normal.

This condition can be caused by a reduced production of insulin, the hormone produced by the pancreas to use sugars and other components of food and turn them into energy, or by the body’s reduced ability to use the insulin it produces.

High blood glucose levels, if not corrected with adequate therapy, can over time favor the onset of chronic complications of the disease, namely, damage to the kidneys, retina, peripheral nerves and cardiovascular system (heart and arteries). It is possible to live with diabetes, but it is essential to know what causes blood sugar to rise or fall in order to keep it as close as possible to normal levels and to avoid or delay the onset and progression of chronic complications that unfortunately worsen the quality of life.

HOW DIABETES ARE RECOGNIZED

People with undiagnosed diabetes often have one or more of these symptoms:

In some cases, there are no noticeable symptoms because blood sugar rises slowly and gradually. This happens especially in type 2 diabetes and means that a person can live for months or years without knowing that they are diabetic and therefore without being adequately treated.

WHO GETS DIABETES

Diabetes is a common disease that affects 3-5% of the general population in Italy. In some countries of northern Europe or North America it can even affect 6-8% of the population. The worrying thing is that the cases of diabetes are constantly increasing, probably due to the increase in obesity and the sedentary lifestyle of the populations.

According to the World Health Organization, in the year 2030 there will be 360 ​​million people with diabetes in the world, compared to 170 million in 2000. This has important repercussions on the lives of patients and their families, and on the health systems that offer assistance. to patients.

Anyone can be affected by diabetes, although the likelihood of developing this disease is higher if you have a first-degree relationship (parents, children, siblings) with a person with diabetes.

HOW DIABETES ARE TREATED

All diabetic patients and their families should have a good understanding of the different aspects of the disease. This is why information meetings offered by diabetes centers or patient associations are important.

It is very important that the person with diabetes is aware of his / her disease, is well acquainted with the drugs he / she may take for diabetes treatment and their main side effects, and is prepared to deal with any unexpected events or particular situations such as occasional illnesses, variations in the mealtimes, travel or pregnancy planning.

A fundamental help in maintaining a good blood sugar comes from the use of instruments for measuring blood glucose. They are simple and reliable tools that allow you to measure blood sugar on capillary blood obtained from the puncture of the fingertip, in total autonomy and at any time of the day.

The indication to carry out blood glucose measurements and the frequency of measurements vary on a case-by-case basis according to the type of diabetes, therapy and the degree of metabolic compensation.

Additionally, people with type 1 or type 2 diabetes should change their lifestyle to have a healthy diet and regular physical activity.

In general, diabetic patients are recommended to:

In patients with type 1 or type 2 diabetes, maintaining good blood glucose control prevents or delays the onset and slows the progression of chronic diabetes complications, i.e. damage to the kidneys, retina, peripheral nerves, or system cardiovascular.

For this reason it is necessary to regularly carry out:

The frequency of visits will be established for each patient based on the type of diabetes and prescribed therapy (lifestyle modification, oral medications or insulin), the degree of metabolic control, the presence of complications or other concomitant diseases .

The regularity of the checks allows to identify the complications of diabetes at a very early stage and, therefore, to start an adequate treatment when it is still possible to limit the organ damage.

TYPE 1 AND 2 DIABETES

Classification of diabetes mellitus

A. Immune-mediated:

B. Idiopathic

A. Genetic defects in cell function
B. Genetic defects of insulin action
C. Pathologies of the exocrine pancreas
D. Endocrinopathies
E. Drug-induced forms
F. Infections (congenital rubella, cytomegalovirus)
G. Genetic syndromes sometimes associated with diabetes
H. Uncommon immune-mediated forms
I. Gestational diabetes

COMPLICATIONS OF DIABETES

Acute complications:

Hypoglycemia is classically defined as a condition in which blood glucose is 50 mg / dl in an adult and 40 mg / dl in a child. Symptoms are characterized by adrenergic activation (sometimes unnoticed or blurred by concomitant neuropathy) already for values ​​between 50 and 60 mg / dl and subsequently neuroglycopenia, which usually begins with glycaemia 50 mg / dl. Neuroglycopenic symptoms begin with mental confusion and, if blood sugar drops below 30 mg / dl, numbness; hypoglycemic coma represents the most severe expression of hypoglycemia and usually occurs for values ​​20 mg / dl.

It is a metabolic acidosis caused by an excessive blood concentration of ketone bodies, produced in excess due to an absolute or relative deficiency of insulin. It is characterized by hyperglycemia (250 mg / dl), hyperketonemia and metabolic acidosis (arterial pH 7.30; HCO3- 15 mEq / L).

Severity

The severity of ketoacidosis is determined by the degree of acidosis and differs in:

In ketoacidosis, peripheral tissues are unable to use glucose for normal metabolism and cause hyperglycemia;

Failure to uptake glucose by hepatic cells stimulates glycogenolysis, while the influx of substrates from lipolysis (free fatty acids) and proteolysis (amino acids) stimulates hepatic gluconeogenesis, with a further increase in the circulating concentration of glucose which contributes to determine hyperglycemia;

Hyperosmolar coma mostly occurs in middle-aged or elderly patients with often misunderstood type 2 diabetes. It is characterized by severe hyperglycemia and hyperosmolarity but not ketosis. It is classically preceded by a period of intense polyuria and polydipsia and often these patients drink sugary drinks to quench their thirst. In some cases it can be precipitated by a reduced fluid intake in lonely or bedridden elderly patients.

Lactic acidosis is divided, according to the Cohen-Woods classification into:

Type A. Determined by hypoperfusion, hypoxia, or increased lactate production;

Type B. Caused by severe metabolic alterations, such as inborn errors of metabolism, excessive adrenergic stimulation or poisoning.

Metformin is undoubtedly one of the most used drugs in the treatment of diabetes mellitus. It is a biguanide with structural similarities to phenformin, withdrawn from the North American market in 1976 for the reporting of several cases of lactic acidosis

In the case of metformin, the data relating to its role in the onset of lactic acidosis are highly controversial. In the case of lactic acidosis, it could be of both types, depending on the condition that determines it.

Chronic complications of diabetes

Chronic complications of diabetes are the leading cause of morbidity and mortality in diabetic patients. They include:

Prevention measures and screening for the early diagnosis of chronic diabetes complications play a role of absolute and primary importance.

Modifiable risk factors

They allow to significantly reduce the risk of developing the main complications of diabetes and to slow down its progression towards the more advanced and disabling stages.

At the same time, the large-scale application of screening, with investigations that are mostly inexpensive, easily accessible and to be carried out periodically in all diabetic patients, makes it possible to recognize the subclinical alterations of early stage diabetic complications at an early stage.

DRUG THERAPY OF DIABETES

Ineffective insulin therapy

Insulin can be administered through syringes, devices called “pens” (which simplify use by limiting the percentage of error) or through insulin pumps.

Subcutaneous administration of insulin differs from physiological secretion in that diffusion occurs into the peripheral circulation rather than directly into the portal circulation, with delayed alignment to the hormone’s secretory homeostasis in response to ingestion of nutrients.

Insulin preparations are classified according to onset, duration of action and peak.

Fast Acting Insulin – Regular Human Insulin (RHI)

It is obtained by biosynthesis from bacteria or yeasts, with the introduction of the human proinsulin gene with the recombinant DNA technique.

An initial delay of about 30 ‘(up to 60’) is followed by a peak after 2-3 hours and a return to baseline levels within 6-8 hours. This affects the time of administration (from 30 ‘to 45’ before a meal).

Ultra-fast acting insulin analogues

They are molecules produced with the recombinant DNA technique and modified in their structure, in order to obtain an absorption as similar as possible to the physiological one.

The action is rapid (starting between 5 ‘and 15’), with a peak between 30-90 ‘and duration of action of about 6 hours. They can be administered immediately to 15 minutes before or even during the meal, allowing greater flexibility in eating patterns and better “coverage” of post-prandial glycemic excursions.

Three ultra-fast acting analogues are currently marketed:

Intermediate-acting insulin

Protaminated insulin (NPH) onset of action between 2-4 hours, peaking between 4-10 hours and varying in duration between 10-16 hours. Its use has now been supplanted by long-acting analogues.

Long-acting insulin analogues

They have a structure that allows a slow and constant release over time, reproducing the physiological basal insulin secretion compared to previous human insulin preparations, with good glycemic control in the intervals between meals and during the night.

Glargine: was the first long-acting analog formulation used in humans. The replacement of Asparagine in the a chain with Glycine and the addition of two Arginine residues in the chain. A constant pharmacokinetic and pharmacodynamic profile is achieved over 24 hours, with onset of action after 1 hour but without a peak.

Detemir: obtained from a genetically modified yeast strain of Saccharomyces Cerevisiae. The duration of action is shorter than insulin Glargine (approximately 17 hours) and requires two daily administrations.

Insulin lispro with protamine (Humalog Basal Kwikpen): derives from the crystallization of Lispro with protamine, which delays the onset of action (between 1 and 4 hours) with a peak at about 6 hours and a duration of action of about 18 hours.

Premixed biphasic insulins

They are preconstituted formulations of two types of insulin in fixed percentages (rapid analogue and rapid analogue with protamine which guarantees an intermediate action).

Other anti-diabetics

To date, two classes of drugs are available that can be classified as GLP-1 agonists:

Both molecules, unlike DPP-4 inhibitors, are characterized by subcutaneous administration (once or twice a day, depending on the molecule). The marketing of long-acting formulations (LAR) with the possibility of weekly administration has recently been approved.

To the class of DPP-4 inhibitors belong molecules which, differently from GLP-1 analogues, are characterized by oral administration (in single or double daily dose). Although with some nuances, regarding receptor selectivity and affinity potency, all the molecules currently available (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) do not seem to have significant differences in clinical efficacy. An important difference that could guide therapeutic choices, especially in often complicated patients such as those affected by T2DM, is the metabolization and excretion of the drug. These are:

These pseudo-carbohydrates (acarbose, voglibose and miglitol), obtained from fermentation processes of microorganisms (for acarbose: Actinoplanes Utahensis), competitively inhibit the alpha-glucosidase enzyme present on the brush border of enterocytes, which hydrolyzes non-absorbable oligosaccharides and the polysaccharides into absorbable monosaccharides. Lacarbose is mainly eliminated in the faeces, partly intact and partly (about 30%) following fermentation of the resident microbiotic flora, it is minimally absorbed.

DIETARY THERAPY FOR DIABETES

Diet is the cornerstone of diabetic therapy and alone can lead to a decrease of 1-2 percentage points in HbA1c. Up to 30% of diabetics could be controlled with diet alone, which associated with physical activity and pharmacotherapy leads them to a goal, improving clinical and metabolic outcomes with a correlated reduction in hospital admissions. Frequent checks with a dietician result in better adherence to the diet. Apparently one-to-one encounters appear to be more effective in low socioeconomic subjects, while group encounters are more effective when associated with adult education principles, group discussions. In selected diabetic groups, peer meetings and web-based education programs further improve knowledge and management of the disease.

Carbohydrates (CHO)

Since the brain needs around 130 g / day of CHO, no diet can predict a lower dose.

A review of diets with CHO content between 4% and 45% showed an improvement in HbA1c and triglyceride levels, but not in total, LDL and HDL cholesterol. Furthermore, diets with very low carbohydrate content would not ensure a sufficient intake of fiber, vitamins and minerals, while they would increase the intake of proteins and fats, which can have harmful effects on the kidneys and cardiovascular outcomes respectively.

Today we tend to place the CHO requirement in the diet at 50-60%, with an optimal intake of 55%. Among carbohydrates, complex ones with a low glycemic index should be preferred (legumes, pasta and bread, preferably whole, fruits from temperate areas). By glycemic index we mean the glycemic levels reached after having eaten a food compared to the glycemic levels after consuming an equal quantity of a reference food which today is bread.

Fat

The fat content in the diet should not exceed 30% of total calories and of these no more than 7% should be saturated fats (animal fats), up to 20% mono-unsaturated fats (vegetable oils); polyunsaturated fats (in particular the omegas of fish oil) must be included in the diet for their action on improving the cardiovascular profile.

Fats are a source of ketone bodies and their excess is the predominant cause of obesity and therefore of insulin resistance. Some types of lipids are co-responsible for diabetic vasculopathy.

Proteins

Currently the recommended dose in the general population is 1-1.5 g / kg / day, corresponding to a requirement of 15-20% of the diet. It does not seem that these quantities and proportions need to be changed in the diabetic. In patients with chronic renal insufficiency the protein intake should be reduced to 0.8 g / kg / day (27-29). Vegetable proteins, white meats and fish should be favored as a source of protein.

In elderly patients, protein supplementation may be envisaged, always keeping an eye on renal function.

Fibers

The intake of soluble fiber in the diet showed a marked improvement in the glycemic profile in patients in all age groups. An average intake of 40 g / day of fiber is recommended in all diets. The fibers contained in whole grains or added with supplements reduce the glycemic peak, slowing down the absorption of carbohydrates and lipids.

Alcohol

There are no differences in recommendations from the general population: a maximum intake of 2 doses / day of alcohol (wine) in women and 3 in men is recommended (1 dose = 10 g of alcohol). Alcohol can mask the symptoms of hypoglycemia, reduces the hepatic production of glucose and increases ketones. The recommended doses of alcohol are associated with a moderate reduction in cardiovascular risk and taken with meals do not modify the risk of hyper or hypoglycemia. Consumption of red wine (but not white wine) appears to have beneficial effects on oxidative stress and inflammation associated with myocardial infarction in diabetic patients and would have protective effects on the kidney.

Vitamins and minerals

If you follow a proper diet, vitamin and mineral supplements are not recommended. Vitamin D supplementation is recommended in patients> 50 years and folic acid in women wishing to become pregnant. Integration may be necessary in special cases: dietary imbalances, patients undergoing bariatric surgery.

Simple sugars

The addition of sucrose up to a maximum of 10% of the daily energy intake is considered acceptable, while a higher quantity increases glycemic levels and triglycerides. Fructose has a trend similar to that of sucrose in quantity and effects: at the same dosages as sucrose it has a slight effect of reducing the levels of HbA1c, at higher doses it increases triglycerides and contributes to weight gain. The fructose contained in fruit and vegetables would have a better effect than that taken in place of sucrose.

Key messages

1. Diet can reduce HbA1c levels by 1-2% (11-22 mmol / mol) and (alone or combined with exercise and drugs) allows therapeutic goals to be achieved in the majority of diabetics.

2. Replacing high-glycemic index foods with low-glycemic index foods has significant clinical significance.

3. The diet should be prescribed by an experienced dietician.

4. Different dietary regimes (primarily the Mediterranean diet) and specific foods have shown improvement of the effects of the diet in the diabetic.

5. The type of carbohydrates, the quantity and distribution of meals throughout the day help in controlling blood sugar and weight.

6. The diet must be adapted to the needs of the individual patient.

PHYSICAL THERAPY IN DIABETES

Lifestyle modification, in particular the implementation of moderate physical activity, is fundamental in the prevention and treatment of diabetes mellitus; yet, recently the DAWN Project Italia, sponsored by the Ministry of Health, IDF and Diabete Italia, through a polling survey showed that physical activity is the least used therapeutic tool for the prevention and therapy of type 2 diabetes mellitus by the Italian diabetic welfare organizations.

The total daily human energy expenditure is also given by thermogenesis due to activity not associated with physical exercise (English acronym NEAT); NEAT represents the energy expenditure of all physical activities other than voluntary and planned ones, eg walking, moving, talking, fidgeting, doing small jobs, etc. In practice, it is the energy expenditure linked to all the ordinary and daily movements that are usually performed; it is intuitive that in the meantime it would be necessary to favor a behavior that gives preference, in daily activities, to the use of one’s muscles, giving up the use of machines.

By “physical activity” we mean the body movement given by the contraction of skeletal muscles, which requires an energy expenditure in excess of the energy expenditure at rest, while “physical exercise” is the body movement programmed, structured and repeated, performed to improve or keep one or more components in good physical shape.

By “aerobic exercise” we mean the execution of rhythmic, repeated and continuous movements of the same large muscle groups for at least 10 minutes each (eg walking, cycling, slow running, swimming, water aerobic exercises and many sports); finally, “resistance exercise” means an activity that uses muscle strength to move a weight or work against a load that offers resistance.

To improve glycemic control, maintain optimal body weight and reduce the risk of cardiovascular disease, at least 150 minutes / week of moderate aerobic physical activity (50-70% of max heart rate) and / or at least 90 minutes / week of exercise are recommended. strenuous physique (> 70% of max heart rate). Physical activity must be spread over at least 3 days / week, avoiding more than 2 consecutive days without activity. All people with type 2 diabetes mellitus should practice regular physical activity, mainly aerobic, with an energy expenditure of 200-300 kcal / day. Aerobic physical activity allows constant but not excessive effort, with less risk of hypoglycemia; the more prolonged the physical activity, the more pronounced the decrease in blood sugar can be; on the other hand, the risk of hypoglycemia decreases the more aerobic the activity is and the better the training. A type 2 diabetic who practices medium intensity physical activity 2-3 times / week does not need, especially if overweight, to vary his diet plan; it exploits an excellent therapeutic tool to reduce insulin-resistance (for a modification of the fat-lean mass ratio), sometimes even allowing to decrease the dosage of hypoglycemic drugs. Furthermore, the constant practice of physical activity favors behavioral changes, which allow other lifestyle corrections (eg cessation of cigarette smoking, greater dietary adherence); all this translates into a reduction in overall cardiovascular risk. the risk of hypoglycemia decreases the more aerobic the activity is and the better the training. A type 2 diabetic who practices medium intensity physical activity 2-3 times / week does not need, especially if overweight, to vary his diet plan; it exploits an excellent therapeutic tool to reduce insulin resistance (for a modification of the fat mass-lean mass ratio), sometimes even allowing to decrease the dosage of hypoglycemic drugs. Furthermore, the constant practice of physical activity favors behavioral changes, which allow other lifestyle corrections (eg cessation of cigarette smoking, greater dietary adherence); all this translates into a reduction in overall cardiovascular risk. the risk of hypoglycemia decreases the more aerobic the activity is and the better the training. A type 2 diabetic who practices medium intensity physical activity 2-3 times / week does not need, especially if overweight, to vary his diet plan; it exploits an excellent therapeutic tool to reduce insulin-resistance (for a modification of the fat-lean mass ratio), sometimes even allowing to decrease the dosage of hypoglycemic drugs. Furthermore, the constant practice of physical activity favors behavioral changes, which allow other lifestyle corrections (eg cessation of cigarette smoking, greater dietary adherence); all this translates into a reduction in overall cardiovascular risk. 2-3 times / week, especially if overweight, he does not need to change his diet plan; it exploits an excellent therapeutic tool to reduce insulin-resistance (for a modification of the fat-lean mass ratio), sometimes even allowing to decrease the dosage of hypoglycemic drugs. Furthermore, the constant practice of physical activity favors behavioral changes, which allow other lifestyle corrections (eg cessation of cigarette smoking, greater dietary adherence); all this translates into a reduction in overall cardiovascular risk. 2-3 times / week, especially if overweight, he does not need to change his diet plan; it exploits an excellent therapeutic tool to reduce insulin-resistance (for a modification of the fat-lean mass ratio), sometimes even allowing to decrease the dosage of hypoglycemic drugs. Furthermore, the constant practice of physical activity favors behavioral changes, which allow other lifestyle corrections (eg cessation of cigarette smoking, greater dietary adherence); all this translates into a reduction in overall cardiovascular risk. sometimes even allowing the dosage of hypoglycemic drugs to be reduced. Furthermore, the constant practice of physical activity favors behavioral changes, which allow other lifestyle corrections (eg cessation of cigarette smoking, greater dietary adherence); all this translates into a reduction in overall cardiovascular risk. sometimes even allowing the dosage of hypoglycemic drugs to be reduced. Furthermore, the constant practice of physical activity favors behavioral changes, which allow other lifestyle corrections (eg cessation of cigarette smoking, greater dietary adherence); all this translates into a reduction in overall cardiovascular risk.

The use of the exercise test is not recommended in asymptomatic individuals at low risk of coronary artery disease who intend to undertake a physical activity program.

In particular, for the person with type 1 diabetes mellitus it is necessary to avoid physical activity in the course of ketase or marked hyperglycemia, to know the procedures to treat possible post-exercise intercurrent or late hypoglycemia due to insulin failure or, conversely, paradoxical hyperglycemia.

In consideration of the greater energy expenditure sometimes also linked to anaerobic work (in the case of young people) often with high physical performance, it is important to know that physical activity determines an increased uptake of glucose in the muscles, which requires appropriate additions of carbohydrates of about 30-60 g / h.

If the glyco-metabolic compensation were not optimal, food additions would be useless, as carbohydrate supplements would be lost in the form of glycosuria.

A conscious moderate physical activity can also be carried out in the presence of any initial diabetes-related complications, to maintain an acceptable quality of life, while avoiding overloading or even damaging the organ where the complications are located.

Finally, the habit of exercising, especially in insulin-dependent young people of a higher cultural level, increases the sense of well-being and safety, reduces the levels of anxiety and depression, and increases self-confidence (self-esteem) and feeling of “power” towards diabetes.