1,2Mandesh Institute of Pharmaceutical Science and Research Center, Mhaswad, Dr. Babasaheb Ambedkar Technological University, Lonere, Raigad MS India- 415509.
3Associate Professor, Shri Ganpati Institute of Pharmaceutical Sciences and Research, Tembhurni, Dr. Babasaheb Ambedkar Technological University, Lonere, Raigad MS India- 413211.
Diabetes mellitus is a serial metabolic disorder characterized by hyperglycemia, which arises due to irregular in insulin secretion, insulin action, or both. This condition affects millions worldwide, making it one of the most pressing health challenges of the 21st century. The number of people living with diabetes rose from 200 million in 1990 to 830 million in 2022. Prevalence has been rising more rapidly in low- and middle-income countries than in high-income countries. The global prevalence of diabetes has been rising rapidly, driven by increasing rates of obesity, sedentary lifestyles, and aging populations. Present review includes basic introduction of diabetes mellitus disease, disease pathophysiology, etiology, sign and symptoms, treatment and prevention control, complications and current disease statistics in India and global scinerio.
The word "diabetes" comes from the Greek word diabainein, which means "to pass through" or "siphon." This reflects the condition's early symptom of excessive urination, as if fluids were "passing through" the body. The term "mellitus" is derived from the Latin word for "honey" or "sweet," referring to the presence of sugar in the urine of people with the condition. Together, Diabetes Mellitus essentially means "siphoning off sweet urine," a characteristic identified in historical medical observations. Diabetes is a long-standing disorder. Diabetes is chronic medical condition characterized by elevated blood glucose levels, which can result from defects in insulin production, insulin action, or both. Effective management and diagnosis of diabetes are crucial to prevent complications. In diabetes patient body risk factors mainly include are obesity, metabolic and cardiovascular disorder. Diabetes belongs to one of the largest global health crises of this century. India has the second-largest number of diabetics worldwide. According to an estimate, over 74 million Indians were diagnosed with diabetes in 2021, and this is expected to rise to over 124 million by 2045 (Statista, 2023). The International Diabetes Federation (IDF) research India predicts 40.9 million patients are observed in 2024. This case is increasing to 69.9 million around in 2025. The number of people with diabetes worldwide has more than doubled during the past 20 years. One of the most worrying features of this rapid increase is the emergence of type 2 diabetes in children, adolescents, and young adults.[1] Increased risk for diabetes is primarily associated with age, ethnicity, family history of diabetes, smoking, obesity, and physical inactivity. Diabetes-related complications including cardiovascular disease, kidney disease, neuropathy, blindness, and lower-extremity amputation are a significant cause of increased morbidity and mortality among people with diabetes, and result in a heavy economic burden on the health care system.[2]
Classification of Diabetes
Blood glucose rises because it cannot be metabolized in the cells, due to lack of insulin production by the pancreas or the inability of the cells to effectively use the insulin that is being produced.[3] The first time WHO (World Health Organization) advertised, in classification of diabetes in 1980, but change in 1985. Diabetes is classified into 3 types as,
Type - I diabetes
In type I diabetes, patient’s pancreas does not make insulin or makes very little insulin. Type I diabetes can affect people at any age, but commonly develops in children and young adults. People living with type I diabetes need daily insulin injections to control their blood glucose levels. This type I diabetes mellitus cases are 5-10% in all cases of diabetes patient. It is indicated by autoimmune breaking up of the pancreatic beta cells. Type I diabetes, control needed a quiet of insulin injection in daily life. Insulin pump remedial treatment is included of control diabetes as well as glucose superintend. This disorder is observed in children, and grown person. Type I diabetes cannot currently be prevented and there is no cure for the condition.
Major symptoms of type I diabetes mainly include abnormal thirst and dry mouth, sudden weight loss, frequent urination, lack of energy, tiredness, constant hunger, blurred vision and bedwetting etc.
Type - II diabetes
Diabetes mellitus is the oldest disorder, it is first described in Ethiopian manuscript in 3000-year-old. And 1936 division of type 1 diabetes and type 2 diabetes are described. Type II diabetes is a chronic metabolic disorder characterized by high blood glucose levels due to the body's ineffective use of insulin, a hormone that regulates blood sugar. Normally, insulin binds to its receptor on the cell membrane, triggering a cascade that allows glucose transporters (GLUT4) to move to the cell surface and take up glucose by different mechanism like Insulin Resistance, Compensatory Hyperinsulinemia, Beta-Cell Dysfunction and also liver contributes to hyperglycemia in type II Diabetes by producing excessive glucose through gluconeogenesis. In Adipose Tissue Dysfunctioning insulin resistance in fat cells results in increased lipolysis (breakdown of fat), releasing free fatty acids into the bloodstream. Elevated free fatty acids further impair insulin action and exacerbate insulin resistance in other tissues like muscle and liver. Incretin hormones (e.g., GLP-1 and GIP), which are released from the gut after eating, enhance insulin secretion. In type II Diabetes, there is reduced incretin effect, contributing to inadequate insulin secretion.[4]
Major symptoms of type II diabetes include Increased Thirst and Frequent Urination, Increased Hunger (Polyphagia), Unexplained Weight Loss, Fatigue, Blurred Vision, Slow-Healing Sores or Frequent Infections, Darkened Skin in Certain Areas (Acanthosis Nigricans), Tingling or Numbness in Hands or Feet (Neuropathy).
Gestational Diabetes
Gestational diabetes mellitus is a form of glucose intolerance diagnosed during pregnancy, typically in the second or third trimester, that is not overt diabetes. It occurs due to the physiological adaptations of pregnancy, combined with a predisposition to insulin resistance and beta-cell dysfunction. It poses risks for both the mother and the newborn and increases the likelihood of developing Type 2 Diabetes later in life.[5]
During pregnancy, placental hormones such as human placental lactogen (hPL), progesterone, cortisol, and prolactin promote insulin resistance to ensure adequate glucose supply to the fetus. Polymorphisms in genes related to glucose metabolism, insulin signaling, and beta-cell function (e.g., TCF7L2, KCNQ1) increase susceptibility. Epigenetic changes during pregnancy (e.g., DNA methylation) can influence metabolic pathways and contribute to GDM. A study showed that maternal insulin sensitivity decreases by 50-60% during the third trimester due to the combined effects of placental hormones. GDM occurs when beta-cells cannot overcome this resistance identified that women with GDM have a reduced first-phase insulin response to glucose, indicating impaired beta-cell compensation. A meta-analysis by Lappas (2010) reported elevated levels of pro-inflammatory cytokines like TNF-? and IL-6 in women with GDM, correlating with increased insulin resistance. Catalano demonstrated that higher pre-pregnancy BMI is associated with increased circulating FFAs, which impair insulin signaling. Kwakernaak (2016) highlighted polymorphisms in TCF7L2 as a significant risk factor for GDM due to its role in beta-cell function and glucose regulation. Epigenetic modifications (e.g., altered DNA methylation in offspring of GDM mothers) have been implicated in intergenerational transmission of metabolic disorders.[6]
Sign and symptoms of diabetes
The outstanding symptoms of diabetes are the polyuria, polydipsia, polyphagia. It is observed in type 1 diabetes and quick evolution are the hyperglycemia, in type 2 diabetes. With loss, fatigue, and body pain are common sign of diabetes. The common sign and symptoms of diabetes.
Frequent Urination (Polyuria): Hyperglycemia exceeds the renal threshold for glucose reabsorption (~180 mg/dL), causing glucosuria (glucose in urine). Glucose draws water osmotically into the urine, leading to osmotic diuresis and increased urine output.
Increased Thirst (Polydipsia): Excessive thirst is a compensatory mechanism as the body attempts to replace lost fluid form frequent Urination. Osmotic diuresis from glucose excretion leads to dehydration and loss of electrolytes. Dehydration triggers the hypothalamus to stimulate thirst via osmoreceptors, resulting in polydipsia.
Increased Hunger (Polyphagia): In type I diabetes, lack of insulin prevents glucose uptake by cells, creating a state of perceived cellular starvation. In type II diabetes, insulin resistance leads to impaired glucose utilization, also triggering hunger signals from the hypothalamus. It is increased the hunger result from the body in capability to exploit the glucose properly, primary feeling of non-stop hunger.
Fatigue: Decreased insulin effectiveness (resistance or deficiency) reduces glucose uptake by cells, leading to insufficient ATP production. Muscle breakdown (proteolysis) and fat breakdown (lipolysis) for alternative energy sources can further contribute to fatigue.
Blurred Vision: High blood glucose levels cause fluid shifts into the lens, altering its shape and refractive index. Chronic hyperglycemia can also damage retinal blood vessels (diabetic retinopathy), leading to vision changes over time.
Slow-Healing Wounds or Frequent Infections:
Hyperglycemia impairs immune function by reducing phagocytosis and neutrophil activity. Poor circulation from vascular damage (microangiopathy) reduces oxygen and nutrient delivery to tissues, delaying wound healing. High glucose levels create a favorable environment for bacterial and fungal growth.
Unexplained Weight Loss:
In type I diabetes, lack of insulin leads to rapid breakdown of fat (lipolysis) and muscle (proteolysis) for energy. In type II diabetes, severe insulin resistance and catabolism contribute to weight loss. Glucosuria also causes calorie loss.
Tingling or Numbness in Hands and Feet (Peripheral Neuropathy):
Chronic hyperglycemia causes damage to peripheral nerves by oxidative stress, inflammation, and sorbitol accumulation via the polyol pathway. Poor circulation exacerbates nerve damage.
Darkened Skin Patches (Acanthosis Nigricans):
Chronic hyperinsulinemia in type 2 diabetes stimulates keratinocyte and fibroblast proliferation via insulin-like growth factor receptors, causing thickened, pigmented skin.
Frequent Infections:
High blood sugar levels weaken the immune system by impairing macrophage and neutrophil function. Hyperglycemia also provides an energy source for pathogens, increasing susceptibility to infections.
Sweet or Fruity-Smelling Breath (Ketoacidosis in Type 1 Diabetes):
In diabetic ketoacidosis, lack of insulin leads to excessive fat breakdown and ketone body production. One ketone, acetone, is exhaled, giving a fruity smell.
Complication of diabetes
Diabetic Ketoacidosis (DKA): Insulin deficiency leads to unregulated lipolysis, resulting in excessive free fatty acids (FFAs). FFAs are converted to ketone bodies (?-hydroxybutyrate, acetoacetate) in the liver, leading to metabolic acidosis. Nausea, vomiting, abdominal pain, fruity breath (from acetone), rapid breathing (Kussmaul respirations), altered mental state are major symptoms. Electrolyte imbalances, cerebral edema, or death if untreated.
Hyperosmolar Hyperglycemic State (HHS):
Severe hyperglycemia (>600 mg/dL) without significant ketoacidosis. Osmotic diuresis causes dehydration and hyperosmolality (>320 mOsm/L), impairing brain function. Symptoms seen in HHS are extreme thirst, confusion, seizures, coma. Severe dehydration, shock, or death if untreated.
Hypoglycemia: Overdose of insulin or oral hypoglycemic agents, missed meals, or excessive exercise causes Hypoglycemia. Sweating, tremors, palpitations, confusion, seizures, or loss of consciousness.
Retinopathy: Hyperglycemia damages retinal capillaries through oxidative stress, advanced glycation end products (AGEs), and VEGF (vascular endothelial growth factor) activation leads to capillary leakage, ischemia, and neovascularization.
Nephropathy: Chronic hyperglycemia causes glomerular hyperfiltration, basement membrane thickening, and podocyte loss may lead to proteinuria, hypertension, and reduced glomerular filtration rate (GFR). In this main symptom include microalbuminuria (early sign), progressing to proteinuria and eventually end-stage kidney disease (ESKD).
Neuropathy: Diabetes mellitus is the most common causes of neuropathy worldwide. Hyperglycemia damages peripheral nerves through sorbitol accumulation (via the polyol pathway), oxidative stress, and ischemia.
Peripheral Neuropathy: Tingling, burning, or numbness in hands/feet.
Autonomic Neuropathy: Affects internal organs, causing gastroparesis, erectile dysfunction, or orthostatic hypotension. Focal Neuropathy: Sudden weakness or pain in specific nerves (e.g., cranial or femoral). Uncontrolled diabetes leads to complications in many organs. Damage to small and large blood vessels and nerves leads to loss of vision and kidney function, heart attacks, strokes, and lower limb amputations. Diabetes causes disability and shortens lives.[3]
Diagnosis of Diabetes:
Diabetes diagnosis involves identifying abnormally high blood glucose levels to ensure timely treatment and prevent complications. Early detection of diabetes is crucial for effective management, as untreated diabetes can lead to significant acute and chronic health issues. Early diagnosis allows for timely intervention, reducing the risk of microvascular complications (like retinopathy, nephropathy, neuropathy) and macrovascular complications (like cardiovascular disease, stroke). Early management of blood sugar levels minimizes symptoms like fatigue, polyuria, and infections, improving daily functioning. Detecting diabetes early avoids costly hospitalizations and treatments for complications. Also identifying prediabetes enables lifestyle modifications to prevent progression to full-blown diabetes.[7]
|
Test |
Preparation |
Sample taken |
Purpose |
|
Fasting plasma glucose (FPG) |
8-hour fasting |
Blood sample |
Screens for prediabetes/diabetes. |
|
Oral Glucose Tolerance Test (OGTT) |
Fasting, glucose drink |
Blood samples pre and post-glucose |
Assesses glucose metabolism and insulin response. |
|
Hemoglobin A1C Test (HbA1C) |
None |
Blood sample |
Diagnoses diabetes; monitors control over time. |
|
Random Plasma Glucose Test (RPG) |
None |
Blood sample |
Quick screening when symptoms are present. |
|
C-Peptide Test |
None |
Blood sample |
Differentiates type I and type II diabetes. |
|
Autoantibody Testing |
None |
Blood sample |
Diagnoses autoimmune forms of diabetes. |
Some Test of diabetes-
1. Fasting plasma glucose (FDG) Test
2. Oral glucose tolerance (OGTT) test.
3. Hemoglobin A1C (HbA1C) test
4. Random plasma glucose test.
1. Fasting plasma glucose test (FPG):-
The Fasting Plasma Glucose (FPG) test is a simple and widely used diagnostic test for diabetes and prediabetes. The patient is instructed to fast for at least 8 hours (no food or drink except water). Avoid heavy physical activity, alcohol, and smoking during the fasting period, as these can affect glucose levels. A healthcare professional collects a venous blood sample from the patient. The blood sample is placed in a tube containing an anticoagulant (e.g., sodium fluoride or EDTA) to prevent clotting and glycolysis (breakdown of glucose in the blood sample). The collected blood sample is sent to a laboratory for glucose measurement by Automated Biochemistry Analyzers using enzymatic methods (e.g., glucose oxidase or hexokinase assay) to measure glucose concentrations or Point-of-Care (POC) Devices like glucometers.
Table: FPG, HbA1C 7 OGTT test levels
|
|
Fasting Plasma Glucose (FPG) |
Hemoglobin A1C Levels |
Oral Glucose Tolerance Test (OGTT) (2-Hour Plasma Glucose Level) |
|
Normal |
Less than 100 mg/dL |
Below 5.7% |
Less than 140 mg/dL |
|
Prediabetes |
100 to 125 mg/dL |
5.7% to 6.4% |
140 to 199 mg/dL |
|
Diabetes Mellitus |
126 mg/dL or higher |
6.5% or over |
200 mg/dL or higher |
2. Oral glucose tolerance test (OGTT):-
The Oral Glucose Tolerance Test (OGTT) is a diagnostic test that evaluates how efficiently the body processes glucose. It is primarily used to diagnose diabetes mellitus, gestational diabetes, and prediabetes. The patient must fast for 8–12 hours before the test (no food or drink except water). Avoid smoking, caffeine, and strenuous physical activity during the fasting period. A healthcare professional collects a fasting blood sample to measure baseline blood glucose levels. The patient drinks a glucose solution (typically 75 grams of glucose dissolved in water for adults). For gestational diabetes screening, a 50-gram or 100-gram glucose solution may be used, depending on the protocol. Blood samples are collected at specific intervals (commonly 30 minutes, 1 hour, and 2 hours after ingestion of the glucose solution). These samples measure how quickly and effectively glucose is cleared from the bloodstream. Patients may resume their regular diet and activities after the test.
3. Haemoglobin A1C test:-
The Hemoglobin A1C (HbA1c) test is a critical diagnostic and monitoring tool for diabetes. It reflects the average blood glucose levels over the past 2–3 months, providing a comprehensive picture of glucose control. An HbA1 level of 6.5% or higher is used to diagnosis diabetes. This test is helpful of observing ongoing management of diabetes. This test helps to assess the severity of hyperglycemia. Higher HbA1c levels correlate with an increased risk of diabetes-related complications like cardiovascular disease, neuropathy, nephropathy, and retinopathy.
Hemoglobin is a protein in red blood cells responsible for carrying oxygen. Glucose binds to hemoglobin in the bloodstream, forming glycated hemoglobin (HbA1c). The HbA1c test measures the percentage of total hemoglobin that is glycated, reflecting average glucose exposure over the lifespan of a red blood cell (~120 days). No fasting or special preparation is required, making it more convenient than fasting glucose or OGTT.
4. Random plasma glucose test (RPG) :-
The Random Plasma Glucose (RPG) Test is a diagnostic tool that measures blood glucose levels at any time of the day, regardless of the last meal. It is particularly useful in identifying hyperglycemia in symptomatic individuals. This test calculated blood glucose level anytime of the day without fasting. Result of 200 mg DL couple with symptoms of diabetes can identified diabetes. Blood glucose levels are regulated by insulin (hormone lowering glucose) and glucagon (hormone increasing glucose). In diabetes, either insufficient insulin production or insulin resistance causes elevated glucose levels, which can be detected by an RPG test. The RPG test plays a critical role in identifying diabetes and hyperglycemia in symptomatic individuals, facilitating early detection in emergency or outpatient settings and aiding in the immediate initiation of treatment to reduce the risk of complications.
Diabetes Prevention:
Effective prevention and control strategies vary depending on the type of diabetes (Type I, Type II, and Gestational Diabetes).
1. Prevention Strategies Type I Diabetes
Genetic and Environmental Research: Type I diabetes cannot currently be prevented as it is an autoimmune condition with strong genetic and environmental components.
Immune Modulation: Immunotherapy or vaccines aimed at slowing or preventing autoimmune destruction of beta cells are under investigation.
Avoiding Environmental Triggers: Reducing exposure to certain viruses or environmental toxins might lower risk in predisposed individuals.
Control Strategies
2. Type II Diabetes
Prevention Strategies
Lifestyle Interventions:
Dietary Changes: Dietary changes are a crucial component of diabetes management. By making informed food choices and adopting healthy eating habits, individuals with diabetes can effectively control their blood sugar levels, reduce the risk of complications, and improve their overall health. Reduction in intake of processed foods, sugary drinks, and high-calorie diets and focus on high-fiber foods, whole grains, lean proteins, and healthy fats is best control strategy for diabetes control.
Physical Activity: Regular physical activity is a vital component of diabetes management. It helps improve insulin sensitivity, regulate blood sugar levels, and reduce the risk of diabetes-related complications.
Weight Management: Losing 5–7% of body weight can significantly reduce the risk of Type II in prediabetic individuals. Weight management is a key aspect of diabetes control, especially for individuals with type 2 diabetes. Excess weight can impair the body's ability to use insulin effectively, leading to higher blood sugar levels.
Screening and Early Intervention: Regular monitoring for individuals at high risk (e.g., family history, obesity, or history of gestational diabetes). Early detection and timely intervention are crucial for effective diabetes management. Regular screening can identify individuals at risk for developing type II diabetes or those who already have the condition without knowing it.
Medications: Medications play a crucial role in managing diabetes, especially for individuals who cannot control their blood sugar levels through lifestyle modifications alone. The type of medication prescribed depends on the specific type of diabetes and individual needs.
|
Sr.No |
Category |
Name of Drug |
Brand |
Mode of action |
|
1 |
Insulin |
Regular insulin |
Humulin R Humalog (lispro) NovoLog (aspart) Apidra (glulisine) Fiasp (aspart) Lyumjev (lispro) Humulin N Lantus (glargine) |
Decrease glucose production and increase peripheral glucose uptake |
|
2 |
Alpha glycoside inhibitor |
Acarbose Miglitor |
Precose Glyset |
Decrease glucose absorption from intestine |
|
3 |
Biguanides |
Metformin phenformin |
Glucophage DBI Fortamet Glumetza Riomet |
Decrease insulin resistance |
|
4 |
Meglitinide |
Repalinide Nateglinide |
Prandin starlix |
Insulin secretagogues |
|
5 |
Sulfonylurea |
Tolbutamide |
Orinase Glimepiride Glyburide Glimiperide |
Block the ATP sensitive potasium channels |
|
6 |
Thiazolidinediones |
Rosiglitazone Pioglitazine |
Avandia Actos |
Increase the insulin sensitivity |
Public Health Initiatives: Public health initiatives play a vital role in preventing and managing diabetes. These initiatives aim to raise awareness, promote healthy lifestyles, and provide access to quality care. Community-based programs promoting healthy eating, active lifestyles, and awareness.
3. Gestational Diabetes (GDM)
Prevention Strategies
Control Strategies
Postpartum Follow-Up: Postpartum follow-up is essential for managing diabetes, especially after gestational diabetes mellitus (GDM), to assess and mitigate long-term risks. Women with GDM require glucose tolerance testing 6–12 weeks postpartum to identify persistent hyperglycemia or prediabetes. Regular monitoring thereafter helps prevent progression to Type 2 diabetes. Lifestyle interventions, including a balanced diet and physical activity, are crucial for sustained glycemic control. Breastfeeding improves insulin sensitivity and lowers maternal blood glucose. Education on risk factors and preventive strategies ensures better adherence. Early postpartum follow-up provides a scientific framework to reduce future complications for both the mother and offspring.
REFERENCES
Akash Narbat, Vaibhav Madane, Namdeo Shinde* Pathophysiology of Diabetes Mellitus with Disease Economics, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 2, 647-657. https://doi.org/10.5281/zenodo.14843855
10.5281/zenodo.14843855
