Classification and pathogenesis of diabetes mellitus
Diabetes mellitus (DM) is the leading pathology of the endocrine apparatus of the pancreas. Several main pathogenetic variants are distinguished:
- Type 1 DM: occurs predominantly in individuals under 30 years of age against the background of genetic predisposition (diabetogenic HLA antigens are detected in 95% of patients). Under the influence of triggers (Coxsackie viruses, rubella, toxic chemicals), an autoimmune reaction is initiated. T-lymphocytes, macrophages, and specific autoantibodies cause immune inflammation of the islets (insulitis). The morphological outcome is the destruction of $\beta$-cells, islet atrophy, and absolute insulin deficiency.
- Type 2 DM: usually develops after 40 years of age, has a polygenic nature, and is closely associated with obesity. It is based on receptor insulin resistance and relative insulin deficiency. The functional exhaustion of $\beta$-cells is promoted by pancreatic lipomatosis and the deposition of local senile amyloid. The protein amylin has direct cytotoxicity toward islet cells.
- MODY diabetes: a rare monogenic form in young individuals with normal body weight, transmitted in an autosomal dominant manner.
- Gestational DM: occurs in pregnant women. It is dangerous due to the development of diabetic macrosomia and the formation of fetal developmental defects (diabetic embryopathy).
- Mitochondrial DM: caused by point mutations in mitochondrial DNA, inherited maternally, and often associated with hearing loss or MELAS syndrome.
Systemic changes and diabetic angiopathies
The key damaging factor in any type of diabetes is hyperglycemia. It activates non-enzymatic protein glycosylation and lipid peroxidation. The morphological basis for most complications is generalized vascular bed damage—diabetic angiopathies (the cause of death in 65–85% of cases).
- Diabetic macroangiopathy: damage to large- and medium-sized arteries. It manifests as early, widespread atherosclerosis and Mönckeberg's medial calcinosis (calcification of the vascular media).
- Diabetic microangiopathy: systemic damage to capillaries and arterioles. It is characterized by marked thickening of basement membranes, plasmorrhagia, and hyalinosis, leading to narrowing up to complete obliteration of the lumen.
These vascular disorders form specific target-organ pathology:
- Kidneys: diabetic nephropathy, the most striking manifestation of which is nodular glomerulosclerosis. On macroscopic examination, the kidneys are finely granular, dense, and symmetrically reduced in size.
- Eyes: diabetic retinopathy. It includes microaneurysms, hemorrhages, and retinal neovascularization. It threatens the development of glaucoma and retinal detachment.
- Nervous system: diabetic neuropathy. It is caused by microangiopathy of the vessels supplying the nerves (vasa nervorum). It leads to segmental demyelination, loss of sensation in the lower extremities, and the formation of neuropathic ulcers in diabetic foot syndrome.
Hormonally active tumors (Insulinomas)
Neoplasms originating from the endocrine cells of the islets of Langerhans are collectively termed insulinomas. These are rare tumors (1–2% of all pancreatic neoplasms). Most often, they have the structure of adenomas. Immunohistochemical examination is necessary to accurately determine the hormonal profile of the tumor.
- Insulinoma: the most frequent neuroendocrine tumor originating from $\beta$-cells. Excess insulin secretion causes severe hypoglycemic episodes. Patients suffer from morning sluggishness, disorientation, epileptiform seizures, and exhibit unmotivated behavior followed by amnesia. All symptoms are rapidly relieved by the administration of glucose.
- Gastrinoma: the second most frequent tumor (derived from G-cells). It is characterized by a malignant course—by the time of detection, up to 75% of patients already have metastases. The release of gastrin provokes Zollinger–Ellison syndrome: marked gastric juice hyperacidity and the formation of multiple "kissing" ulcers of the stomach and duodenum, prone to bleeding and perforation. In half of the cases, gastrinoma is associated with multiple endocrine neoplasia type 1 (MEN-1) syndrome.
- Glucagonoma: a tumor developing from $\alpha$-cells.
Briefly: answers to topical questions
What changes occur in the fundus in diabetic retinopathy?
In diabetic retinopathy, vascular anomalies, hemorrhages, and optic nerve changes occur in the fundus.
- Microaneurysms—detected in retinal capillaries and venules.
- Hemorrhages—include microhemorrhages, small intraretinal, preretinal, and vitreal hemorrhages (hemophthalmos).
- Exudates—"hard" and "soft" ("cotton wool") foci are formed.
- Vascular anomalies—intraretinal microvascular abnormalities (IRMA), beading and deformation of venules, neovascularization of the optic disc and retina are observed.
- Edema—perivascular edema, macular edema, and optic disc edema develop.
- Severe complications—tractional retinal detachment, fibrous proliferation, dystrophic and atrophic changes of the optic nerve.
What types of hormonally active pancreatic tumors exist, and from what cells do they develop?
Hormonally active pancreatic tumors include:
- Insulinoma—hypersecretes insulin.
- Glucagonoma—hypersecretes glucagon.
- VIPoma—hypersecretes vasoactive intestinal peptide.
- Somatostatinoma—hypersecretes somatostatin.
- Gastrinoma—associated with Zollinger–Ellison syndrome.
- Pancreatic polypeptideoma.
- Calcitoninoma—hypersecretes calcitonin.
- ACTHoma—hypersecretes ACTH.
The cited sources do not explicitly state the cellular origin of these tumors. The pancreatic islets contain insulin-secreting B-cells and glucagon-secreting A-cells.
What clinical manifestations are characteristic of glucagonoma?
Glucagonoma is characterized by:
- Necrolytic migratory erythema (necrotic rash).
- Diabetes mellitus or impaired glucose tolerance.
- Weight loss, cachexia, anemia.
- Mucosal lesions.
The clinical presentation of hyperinsulinism in insulinoma is easy to remember as a "glucose hangover": morning sluggishness, unmotivated behavior, retrograde amnesia. It is also "treated" simply—with sweets (intravenous glucose).
Class and exam questions
What is the difference between MODY diabetes and classical type 2 diabetes mellitus?
MODY diabetes is a monogenic disease with an autosomal dominant inheritance pattern. Unlike polygenic type 2 diabetes, it occurs at a young age, patients maintain a normal body weight, and lipid metabolism disorders are practically absent.
What is the role of amylin in the development of pancreatic pathology?
Amylin is a polypeptide produced by $\beta$-cells. In elderly patients with type 2 diabetes, it forms local senile amyloid. It acts as an insulin antagonist, increases insulin resistance, and exerts a direct toxic effect on islet cells, leading to their atrophy.
What is Zollinger-Ellison syndrome?
This is a clinical syndrome that develops in gastrinoma. The tumor uncontrollably secretes gastrin, which leads to pronounced gastric juice hyperacidity and the formation of severe, recurrence- and complication-prone multiple ulcers of the stomach and duodenum.
What else to study on this topic
- Morphological and clinical characteristics of MODY diabetes variants (types 1–5)
- Pathogenesis of fetal disorders in gestational diabetes (diabetic macrosomia and embryopathy)
- Stages of development of diabetic retinopathy: from non-proliferative to proliferative form
- Comparative morphology of clinical and pathogenetic variants of diabetic foot syndrome (ischemic and neuropathic)
- Pathogenesis of Mauriac syndrome in children with decompensated type 1 diabetes
Master the entire topic in the "Pathological Anatomy" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Pathology of the Endocrine Pancreas" and 4,414 more pages on the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 153 video lessons on the subject
Other topics in Chapter 19: Diseases of the Endocrine System
Free video lessons: pathological anatomyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.