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ETIOLOGICAL FACTORS AND TREATMENT PRINCIPLES OF DIABETES
MELLITUS
Panjiyev Jonibek Abdumajidovich
Department of Fundamental Medical Sciences of the Asian International University.
Bukhara, Uzbekistan.
https://doi.org/10.5281/zenodo.15284271
Abstract.
Diabetes mellitus (DM) is a long-standing, complicated, and non-transmissible
endocrine ailment that is growing rapidly and has posed clinical challenges globally, often
linked with threats related to complicated metabolic development in patients. It is marked by
elevated glucose and lipids in the blood as well as oxidative stress, which culminate in chronic
complications involving diverse organs, mainly the kidneys, eyes, nerves, and blood vessels,
among others, in the div. The article provides a comprehensive overview of the underlying
causes and management strategies of diabetes mellitus. It explores both genetic and
environmental factors contributing to the development of type 1 and type 2 diabetes, including
autoimmune processes, insulin resistance, obesity, and lifestyle influences. The article also
outlines current treatment principles, emphasizing individualized care that integrates lifestyle
modifications, pharmacological interventions, and patient education. Special attention is given
to the role of emerging therapies and the importance of glycemic control in preventing
complications. This article is valuable for healthcare professionals and students seeking a
foundational understanding of diabetes etiology and evidence-based management.
Keywords:
hyperglycemia, Diabetes mellitus, insulin, MODY, insulin resistance.
ЭТИОЛОГИЧЕСКИЕ ФАКТОРЫ И ПРИНЦИПЫ ЛЕЧЕНИЯ САХАРНОГО
ДИАБЕТА
Аннотация.
Сахарный диабет (СД) — это хроническое, сложное и
неинфекционное эндокринное заболевание, которое быстро распространяется и
представляет собой клиническую проблему во всём мире. Оно часто связано с рисками,
обусловленными сложными метаболическими нарушениями у пациентов. Заболевание
характеризуется повышенным уровнем глюкозы и липидов в крови, а также
оксидативным стрессом, что приводит к хроническим осложнениям со стороны
различных органов, в первую очередь почек, глаз, нервной системы и кровеносных сосудов.
Статья предоставляет всесторонний обзор причин возникновения и стратегий
лечения сахарного диабета. Рассматриваются как генетические, так и экологические
факторы, способствующие развитию диабета 1 и 2 типа, включая аутоиммунные
процессы, инсулинорезистентность, ожирение и образ жизни. Также изложены
современные принципы лечения с акцентом на индивидуальный подход, включающий
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изменение образа жизни, медикаментозную терапию и обучение пациентов. Особое
внимание уделено новым методам лечения и значению контроля уровня глюкозы в крови
для предотвращения осложнений. Данная статья будет полезна медицинским
специалистам и студентам, стремящимся получить базовые знания об этиологии
сахарного диабета и его лечении, основанном на доказательной медицине.
Ключевые
слова:
гипергликемия,
сахарный
диабет,
инсулин,
MODY,
инсулинорезистентность
Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the
phenotype of hyperglycemia. Several distinct types of DM are caused by a complex interaction
of genetics and environmental factors. Depending on the etiology of the DM, factors contributing
to hyperglycemia include reduced insulin secretion, decreased glucose utilization, and increased
glucose production. The metabolic dysregulation associated with DM causes secondary
pathophysiologic changes in multiple organ systems that impose a tremendous burden on the
individual with diabetes and on the health care system. It also predisposes to cardiovascular
diseases. With an increasing incidence worldwide, DM will be a leading cause of morbidity and
mortality for the foreseeable future. As reported by World Health Organization (WHO), DM is
an outbreak prone to high malaise and death. Globally, approximately 387 million persons are
affected by this disorder and it is estimated to be more than 640 million by 2040.
Etiologic Classification of Diabetes Mellitus:
I. Type 1 diabetes (beta cell destruction, usually leading to absolute insulin deficiency)
A. Immune mediated
B. Idiopathic
II. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin
deficiency to a predominantly insulin secretory defect with insulin resistance)
III. Other specific types of diabetes
A. Genetic defects of beta cell function characterized by mutations in
1. Hepatocyte nuclear transcription factor (HNF) 4α (MODY 1)
2. Glucokinase (MODY 2)
3. HNF-1α (MODY 3)
4. Insulin promoter factor-1 (IPF-1; MODY 4)
5. HNF-1β (MODY 5)
6. NeuroD1 (MODY 6)
7. Mitochondrial DNA
8. Subunits of ATP-sensitive potassium channel
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9. Proinsulin or insulin
B. Genetic defects in insulin action
1. Type A insulin resistance
2. Leprechaunism
3. Rabson-Mendenhall syndrome
4. Lipodystrophy syndromes
C. Diseases of the exocrine pancreas—pancreatitis, pancreatectomy, neoplasia, cystic
fibrosis, hemochromatosis, fibrocalculous pancreatopathy, mutations in carboxyl ester lipase
D.
Endocrinopathies
acromegaly,
Cushing’s
syndrome,
glucagonoma,
pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma
E. Drug or chemical induced—glucocorticoids, vacor (a rodenticide), pentamidine,
nicotinic acid, diazoxide, β-adrenergic agonists, thiazides, hydantoins, asparaginase, α-
interferon, protease inhibitors, antipsychotics (atypicals and others), epinephrine.
F. Infections—congenital rubella, cytomegalovirus, coxsackievirus.
G. Uncommon forms of immune-mediated diabetes-“stiff-person” syndrome, anti-insulin
receptor antibodies.
H. Other genetic syndromes sometimes associated with diabetes-Wolfram’s syndrome,
Down’s syndrome, Klinefelter’s syndrome, Turner’s syndrome, Friedreich’s ataxia,
Huntington’s chorea, Laurence-Moon-Biedl syndrome, myotonic dystrophy, porphyria, Prader-
Willi syndrome
IV. Gestational diabetes mellitus (GDM)
Other Types of DM:
Other etiologies for DM include specific genetic defects in insulin secretion or action,
metabolic abnormalities that impair insulin secretion, mitochondrial abnormalities, and a host of
conditions that impair glucose tolerance (Table 19-1). Maturity-onset diabetes of the young
(MODY) is a subtype of DM characterized by autosomal dominant inheritance, early onset of
hyperglycemia (usually>25 years), and impairment in insulin secretion (discussed below).
Mutations in the insulin receptor cause a group of rare disorders characterized by severe
insulin resistance. DM can result from pancreatic exocrine disease when the majority of
pancreatic islets are destroyed. Cystic fibrosis–related DM is an important consideration in this
patient population.
Hormones that antagonize insulin action can also lead to DM. Thus, DM is often a feature
of endocrinopathies such as acromegaly and Cushing’s disease. Viral infections have been
implicated in pancreatic islet destruction but are an extremely rare cause of DM.
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A form of acute onset of type 1 diabetes, termed fulminant diabetes, has been noted in
Japan and may be related to viral infection of islets.
In addition, There are several risk factors associated with diabetes. These risk factors
contribute significantly to the progression of diabetes. They include but not limited to age;
weight; family history of diabetes; smoking and race/ethnicity (Asiimwe et al., 2020; Noh et al.,
2018). While T1DM is mostly found in the young, T2DM is an adult-related condition. The risk
of T2DM increases with age which is due to the deficiency of insulin secretion which develops
with age, and growing insulin resistance caused by a change in div composition. Increase in
div weight which leads to obesity is closely associated with diabetes in a condition termed
diabesity.
This is because increase in div weight leads to increased insulin resistance.
According to the FDA, smokers are 30 to 40% more likely to come down with T2DM
than nonsmokers. Smoking can also increase insulin resistance which makes the patients require
more insulin for the control of their sugar level [19]. Diabetes is hereditary. Those with the
family history are advised to adhere to lifestyles that reduce the risk of developing diabetes.
Treatment:
The treatment principles of diabetes mellitus (DM) aim to achieve and maintain optimal
blood glucose levels, prevent complications, and enhance the quality of life. The approach
depends on the type of diabetes and the individual patient’s needs. Below are the core principles:
1. Lifestyle Modifications
Dietary Management:
-Emphasize a balanced diet with controlled carbohydrate intake.
-Focus on high-fiber foods, lean proteins, healthy fats, and low glycemic index foods.
-Avoid sugary beverages and processed foods.
Physical Activity:
-Regular exercise (e.g., 150 minutes of moderate aerobic activity per week) improves
insulin sensitivity and helps manage weight.
Weight Management:
-Encourage weight loss in overweight or obese patients to improve glycemic control.
2. Pharmacologic Therapy
Type 1 Diabetes Mellitus (T1DM):
Insulin therapy is mandatory:
-Basal-bolus insulin regimen or insulin pumps.
-Regular monitoring of blood glucose levels.
Type 2 Diabetes Mellitus (T2DM):
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Oral or injectable antihyperglycemic agents are often the first-line therapy:
-Metformin: First-line medication for most patients.
-Other options: SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or
sulfonylureas.
-Insulin therapy may be required in advanced stages or during acute illness.
Gestational Diabetes:
-Lifestyle changes and, if needed, insulin or metformin.
3. Monitoring and Glycemic Targets
Self-Monitoring of Blood Glucose (SMBG):
-Frequent monitoring to assess glucose control, especially for those on insulin.
HbA1c Testing:
-Target levels: <7% for most patients, but individualized based on age, comorbidities, and
risk of hypoglycemia.
Continuous glucose monitoring (CGM) may be beneficial for some patients.
4. Management of Comorbidities
Hypertension: ACE inhibitors or ARBs are commonly used.
Dyslipidemia: Statins are often recommended.
Obesity: GLP-1 receptor agonists or bariatric surgery in selected cases.
Prevention of Complications:
-Regular screening for retinopathy, nephropathy, and neuropathy.
-Foot care to prevent ulcers and infections.
5. Patient Education and Support
Provide comprehensive education on disease management.
Psychological support to address stress, anxiety, or depression.
Encourage active participation in care and goal setting.
6. Prevention of Acute and Chronic Complications
Acute Complications:
-Prevent hypoglycemia with proper dosing and meal planning.
-Manage diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS)
promptly.
Chronic Complications:
-Control glucose, blood pressure, and lipids to reduce risks of cardiovascular disease,
kidney disease, and nerve damage.
7. Regular Follow-Up
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Routine visits to monitor progress, adjust treatment plans, and address new issues.
Coordination with a multidisciplinary team, including endocrinologists, dietitians, and
diabetes educators.
Effective diabetes management relies on a tailored approach that considers the patient’s
age, type of diabetes, lifestyle, comorbid conditions, and preferences.
Conclusion:
Diabetes mellitus remains a major global health concern with multifactorial
etiology and complex pathophysiology. Understanding the diverse causes—from genetic
predispositions to lifestyle and environmental triggers—is essential for effective prevention and
early diagnosis. While treatment strategies continue to evolve, a patient-centered approach that
combines lifestyle modifications, pharmacological therapy, and continuous monitoring remains
the cornerstone of management. Advances in research and technology hold promise for more
personalized and effective interventions, but prevention through public awareness and early
intervention remains key. A comprehensive understanding of both the etiological factors and
treatment principles is critical for reducing the burden of diabetes and improving long-term
outcomes.
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