Insulin resistance

Role in metabolic syndrome and comorbidity

Insulin resistance is a dominant feature and fundamental basis of metabolic syndrome. In adolescents with type 2 diabetes mellitus (T2DM), this condition is associated with the development of a whole complex of comorbid conditions:

• Abdominal obesity.
• Arterial hypertension (AH).
• Severe dyslipidemia.
• Appearance of microalbuminuria.
• Non-alcoholic fatty liver disease (NAFLD).
• A specific skin marker — Acanthosis nigricans.

Obesity itself is a potent risk factor characterized by a chronic course and periodic exacerbations. It inevitably leads to early disability and increases the overall mortality rate of patients as early as childhood and adolescence.

Pathogenesis and vicious cycles

The interaction of key links in the loss of sensitivity to insulin forms closed pathological cycles. Several triggers are distinguished in the pathogenesis (including 21-hydroxylase deficiency). For instance, hypogonadism directly contributes to the development of obesity. Hypercorticism has a direct impact on the development of overweight, arterial hypertension, and insulin resistance itself. Adrenomedullary insufficiency also stimulates excessive insulin secretion.

The cascade of pathological reactions develops according to the following scenario:

1. Insulin resistance of peripheral tissues develops.
2. Compensatory hyperinsulinemia occurs (the pancreas increases hormone secretion to overcome the tissue barrier).
3. Excess insulin stimulates massive fat tissue accumulation (obesity) and causes hyperlipidemia.
4. Obesity causes arterial hypertension and further exacerbates hormone insensitivity, completing the vicious circle.

In addition, insulin resistance has a bidirectional relationship with polycystic ovary syndrome (PCOS) and hyperandrogenism. The final clinical outcomes of these processes are prediabetes (impaired fasting glucose or impaired glucose tolerance), clinically manifest type 2 DM, severe hyperlipidemia, and endothelial dysfunction.

Systemic complications of obesity

The pathology is not limited to metabolic shifts alone. Against the background of insulin resistance and obesity, systemic somatic and vegetative disorders are observed:

• Respiratory system: respiratory failure develops. The main mechanism here is a significant decrease in lung excursion due to the high standing of the diaphragm dome.
• Digestive tract: the evacuation function of the stomach and intestines suffers, manifesting as persistent constipation and symptoms of irritable bowel syndrome.
• Reproductive system (in children): in girls, the pathology disrupts the vegetative-somatic functions of the ovaries, causing early appearance of secondary sexual characteristics and menstrual cycle disorders. In boys, both pathological acceleration and sharp deceleration of reproductive organ development are possible.
• Nervous system: in obese children, due to restricted physical activity, there is a pronounced adverse effect on the development of higher nervous activity (HNA), and vegetative-vascular dystonia is formed.

Pathophysiological rationale for therapy selection

Type 2 diabetes mellitus is considered a heterogeneous pathology. Differences in development mechanisms dictate completely different approaches to patient management:

• Option A (elderly individuals without obesity): the pathogenesis is based on insufficient production of endogenous insulin (absolute or relative hypoinsulinemia). The therapeutic goal is to stimulate the secretion of one's own hormone.
• Option B (individuals with overweight): the disease occurs against the background of high blood hormone concentrations and hyperglycemia. The basis of the metabolic syndrome here is insulin resistance. The therapeutic goal is to overcome peripheral tissue resistance (increase their sensitivity to insulin) and break the cascade of reactions leading to cardiovascular catastrophes.

Class and exam questions

What else to study on this topic

• Mechanisms of endothelial dysfunction formation in metabolic syndrome.
• The impact of classical forms of 21-hydroxylase deficiency on the development of metabolic complications.
• Pathogenetic links between hyperinsulinemia, hyperandrogenism, and polycystic ovary syndrome (PCOS).
• Stages of carbohydrate metabolism disorders: from impaired fasting glycaemia (IFG) to manifest type 2 diabetes.
• Features of the course and potential complications of type 2 diabetes mellitus in patients without overweight.

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.