Acute and Chronic Complications of Diabetes: A Complete Guide.

  

 

 

Introduction

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by high blood sugar (hyperglycemia) due to defects in insulin secretion, insulin action, or both. Globally, diabetes affects millions of people and is one of the leading causes of death and disability. Diabetes Mellitus persistent hyperglycemia is linked to end-organ damage, malfunction, and failure, including blood vessel, neurological, kidney, retina, and heart damage. In 2011, the International Diabetes Federation (IDF) projected that 366 million people worldwide had diabetes mellitus, and by 2030, that number is expected to increase to 552 million. Pakistan was ranked seventh on the WHO's list of countries with a high frequency of polygenic diseases [1]. According to recent research on prevalence, around four.7 million people are suffering from polygenic illness. The complications associated with diabetes are a significant cause of morbidity, reducing the quality of life for many individuals. Understanding these complications is essential for healthcare providers and patients to mitigate risks and improve outcomes.

Treatment for diabetes mellitus is based on the etiology and is primarily divided into type 1 and type 2 diabetes mellitus. Individuals with coexisting genetic predispositions or concurrent drug therapy, such as corticosteroids, are more likely to have hyperglycemia. The American Diabetes Association (ADA) has recently recommended HbA1c testing as a screening tool for diabetes mellitus. Strong correlations have been found in observational studies that indicate poor clinical outcomes both acutely in intensive care settings and in chronic hyperglycemia. Tight glycemic control in these settings is controversial because it increases the risk of hypoglycemia and may increase morbidity and mortality. In critically ill patients, a glucose range of 140–180 mg/dL (7.8–10.0 mmol/L) should be maintained through continuous intravenous insulin infusion [2].

 

 

 Types of Diabetes Mellitus

 

 Type 1 Diabetes

Type 1 diabetes is an autoimmune condition where the body's immune system attacks insulin-producing cells in the pancreas. This leads to an absolute deficiency of insulin, and people with Type 1 diabetes must rely on insulin injections for survival.

Type-1 diabetes (T1D), previously recognized as juvenile diabetes or insulin-dependent diabetes, is a condition caused by autoimmune disease in which the islets of Langerhans' beta cells that make insulin are destroyed, causing the pancreas to produce little or no insulin.

Causes & Risk Factors of Type-1 Diabetes:

Autoimmune Destruction: The immune system mistakenly attacks and destroys pancreatic beta cells.

Genetic Predisposition: Linked to HLA-DR3/DR4 genes (higher risk in Caucasians).

Environmental Triggers:

• Viral infections (e.g., enteroviruses, Coxsackie B).
• Early exposure to cow’s milk (controversial).
• Vitamin D deficiency.

No Direct Link to Lifestyle: Unlike Type 2, obesity/diet does not cause T1D.

 

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 Type 2 Diabetes

Type 2 diabetes is the most common form of diabetes. It is characterized by insulin resistance and relative insulin deficiency. Unlike Type 1, Type 2 can often be managed with lifestyle changes and medications, although some individuals require insulin therapy over time.

Both type 1 and type 2 diabetes can manifest during childhood or adulthood. Type 2 diabetes is more prevalent among older adults; however, there has been an increase in cases among younger individuals, largely due to the growing number of obese children. While type-II diabetes is not curable, it can be effectively managed through regular exercise, a balanced diet, and weight reduction. If lifestyle changes are insufficient to regulate blood sugar levels, diabetes medications orinsulin therapy may be necessary.

What are the risk factors for type 2 diabetes?

Type 2 diabetes can manifest at any age, including during childhood. The likelihood of developing this condition increases if you:

- are overweight or suffer from obesity.

– are 35 years of age or older. While children and adolescents can also be diagnosed with type 2 diabetes, the risk escalates with age.

- have a family history of diabetes. - belong to certain ethnic groups, including African American, American Indian, Asian American, Hispanic/Latino, or Pacific Islander.

- lead a sedentary lifestyle, whether due to physical limitations, inactivity, or occupations that require prolonged sitting.

- have pre-diabetes.

 - have experienced gestational diabetes during pregnancy or have given birth to a child weighing 9 pounds or more.

 

 Gestational Diabetes

Gestational diabetes arises during pregnancy and, if not effectively managed, can result in complications for both the mother and the child. Additionally, women who have gestational diabetes face a heightened risk of developing Type 2 diabetes in the future.

 

 Secondary Diabetes

Secondary diabetes results from other medical conditions or the use of certain medications, such as steroids, which affect insulin production or action.

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Stress and diabetes mellitus

Diabetes-related persistent hyperglycemia may be exacerbated by stress. It has long been established that stress significantly affects metabolic activity. The fight-or-flight response is primarily responsible for energy mobilization. Blood glucose levels may rise as a result of the hormones that stress triggers to release. While this is important for adaptation in a healthy organism, in diabetics, stress-induced elevations in glucose cannot be adequately digested due to a partial or total absence of insulin. Furthermore, diabetes may cause abnormalities in the regulation of these stress hormones. Contradictory data, however, characterizes the impact of stress on type I diabetes. While some human research conducted in the past has shown that stress may be a contributing factor in type I diabetes, studies conducted on animals have demonstrated that different types of stressors may either cause or prevent various experimental models of the illness.
Human research has demonstrated that stress can either exacerbate hypo- or hyperglycemia or have no effect at all on a patient's glycemic condition in the case of existing diabetes. A large portion of this perplexity might be attributed to autonomic neuropathy, which is prevalent in type I diabetes. On the other hand, there is more reliable data that links stress to type II diabetes. A substantial amount of research on animals supports the idea that stress consistently causes hyperglycemia in type II diabetes, despite the paucity of human studies on the subject. Moreover, there is growing proof that autonomic processes have a role in the pathogenesis of this illness in both people and animals [3].

 

Complications of Diabetes Mellitus

Blood vascular issues are the main cause of diabetic complications. Long-term elevated glucose levels lead to the narrowing of the small and major blood arteries. Numerous body areas receive less blood flow due to constriction, which might cause issues. There are several reasons why blood vessels narrow, including:

The accumulation of complex sugar-based compounds in the walls of tiny blood vessels results in their thickening and eventual leakage.
Inadequate management of blood glucose levels raises blood fat levels, which leads to atherosclerosis and reduced blood flow in the bigger blood vessels.

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 Acute Complications of Diabetes Mellitus

 

 Diabetic Ketoacidosis (DKA)

DKA is a life-threatening condition most commonly seen in Type 1 diabetes. Individuals with type 2 diabetes are also at risk of developing diabetic ketoacidosis (DKA).  It occurs when there is a severe insulin deficiency, leading to the breakdown of fats for energy and the accumulation of ketones, an excessive and rapid production of ketones can lead to their accumulation in the body, reaching hazardous levels, causing acidosis.

The primary triggers for diabetic ketoacidosis (DKA) include non-adherence to treatment, newly diagnosed diabetes, and various acute medical conditions. Pneumonia and urinary tract infections are the most frequently encountered types of infections associated with DKA. Additionally, factors such as alcohol misuse, physical trauma, pulmonary embolism, and myocardial infarction can lead to the onset of DKA. Medications that influence carbohydrate metabolism, including corticosteroids, thiazide diuretics, sympathomimetic agents, and pentamidine, May also contribute to the development of DKA. Furthermore, both conventional and atypical antipsychotic medications can induce hyperglycemia and, in rare cases, DKA.

According to several research conducted in various regions, the incidence of diabetic ketoacidosis varies from 0 to 56 per 1000 person-years. Women and non-White people are more likely to have DKA. Patients who use injectable insulin have a higher incidence than those who use subcutaneous insulin infusion pumps.

 Hyperosmolar Hyperglycemic State (HHS)

HHS is a dangerous complication typically seen in older adults with Type 2 diabetes. It involves extremely high blood sugar levels, leading to severe dehydration and, if untreated, can result in coma or death.

Extreme thirst, frequent urination, and confusion are some of the symptoms of hyperosmolar hyperglycemic State (HHS), which is an emergency that needs to be treated right away because it can be fatal, if left, untreated. HHS occurs when extremely high blood sugar causes life-threatening dehydration and highly concentrated blood (high osmolality); it also involves a lack of insulin, though the person usually still produces enough insulin to stop the production of ketones; and it is typically accompanied by an underlying condition, such as an infection, that is also contributing to the elevated blood sugar.

 

 Hypoglycemia

Hypoglycemia, or low blood sugar, can occur in individuals taking insulin or certain diabetes medications. Symptoms include shakiness, confusion, and in severe cases, unconsciousness or seizures.

 

 Chronic Complications of Diabetes Mellitus

 

 Micro-vascular Complications

 Diabetic Retinopathy

Diabetic retinopathy affects the eyes and is a leading cause of blindness in adults. High blood sugar damages the blood vessels in the retina, leading to vision loss.

How diabetes can affect the eyes

The retina, situated at the posterior part of the eye, consists of light-sensitive cells that play a crucial role in converting light into electrical impulses. These impulses are sent to the brain, which interprets them as visual images. Additionally, the retina requires a continuous blood supply, which it obtains through a network of small blood vessels.

Prolonged elevated blood sugar levels can lead to damage in blood vessels. Nevertheless, it typically requires several years for diabetic retinopathy to progress to a point where it poses a risk to vision. To reduce the likelihood of these occurring, individuals with diabetes should:

-         maintain control over their blood sugar, blood pressure, and cholesterol levels,

-         participate in diabetic eye screening appointments, which are available to all individuals with diabetes aged 12 and older to identify and address any issues at an early stage.

 

 Diabetic Nephropathy

Diabetic nephropathy affects the kidneys, causing progressive damage that can eventually lead to kidney failure and the need for dialysis or a kidney transplant.

As an early indicator of kidney impairment, excessively high protein levels (albumin) in the urine of diabetics are typically checked by doctors. People are often given drugs that slow the progression of kidney damage at the first signs of complications with their kidneys. Examples of these drugs include angiotensin-converting enzyme (ACE) inhibitors, sodium-glucose co-transporter-2 (SGLT2) inhibitors, or angiotensin II receptor blockers (ARBs).

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 Diabetic Neuropathy

Diabetic neuropathy is nerve damage caused by prolonged high blood sugar levels. It can affect the peripheral nerves, leading to pain and numbness, or the autonomic nerves, leading to blood pressure regulation and digestion issues.

There are several ways this can occur, and they all appear to be connected to sustained high blood sugar levels. To prevent this condition, it is advisable to partner with your doctor in managing your blood sugar. Your physician may mention the four types of neuropathy associated with diabetes: peripheral, autonomic, proximal, and focal.

 

Liver damage in diabetes

Diabetes patients frequently also have steatotic liver disease, commonly known as fatty liver disease, which is characterized by abnormal fat deposits accumulating in the liver. Sometimes, cirrhosis and other more severe liver diseases might develop from steatotic liver disease. When there are abnormalities in liver imaging or blood test results that indicate abnormal liver function, doctors diagnose liver issues. A liver biopsy is then performed to confirm the diagnosis. Treating excessive cholesterol, controlling blood sugar levels, and losing weight can all be beneficial.

 

 

 Macro-vascular Complications

 Cardiovascular Disease (CVD)

Diabetes significantly increases the risk of cardiovascular disease, including heart attacks, strokes, and atherosclerosis, which is the hardening of the arteries.

A significant connection exists between diabetes mellitus (DM) and cardiovascular disease (CVD), which is the foremost cause of health complications and fatalities among diabetic individuals. Common cardiovascular risk factors, including obesity, hypertension, and dyslipidemia, are prevalent in patients with DM, thereby increasing their risk of cardiac events. Moreover, extensive research has revealed biological mechanisms related to DM that independently raise the likelihood of CVD in these patients. As a result, it is crucial to target cardiovascular risk factors in those with DM to lessen the long-term cardiovascular complications associated with the disease.

 

Infections in diabetes

Diabetes frequently causes bacterial and fungal infections, usually affecting the mouth and skin. When blood glucose levels are high, white blood cells are less able to combat infections. In patients with diabetes, infections typically manifest as more serious conditions that require more time to heal. Infections can occasionally be the initial indication of diabetes.
Candidiasis, an infection of the yeast, is one such illness. Normally harmless, candida yeast is a common habitant of the mouth, digestive system, and vagina. However, Candida can overgrow on mucous membranes and moist skin regions in diabetics, leading to rashes in those locations.
Due to inadequate blood flow to the skin, diabetics are also more susceptible to foot and leg ulcers and infections. These wounds heal far too slowly or not at all. Infections from wounds that do not heal frequently lead to gangrene, or tissue death, and osteomyelitis, or bone infection. Amputating the foot or a portion of the leg could be necessary.

 

 Peripheral Arterial Disease (PAD)

Peripheral arterial disease (PAD) occur when the arteries in the limbs become narrowed, reducing blood flow and leading to pain, ulcers, or even gangrene in severe cases.

A variety of the risk factors can be controlled to minimize the risk of developing peripheral artery disease (PAD) or to slow its progression. For individuals with diabetes, it is particularly important to regulate blood glucose levels. Regular exercise is also vital. In certain situations, specialized footwear and medications may be necessary. Additionally, it is essential to stop smoking and manage high blood pressure and cholesterol levels effectively.

 

 Cerebrovascular Disease

Cerebrovascular disease involves the blood vessels supplying the brain, increasing the risk of stroke in diabetic individuals.

 

 Diabetic Retinopathy: Causes, Progression, and Impact

Chronic hyperglycemia leads to the weakening of retinal blood vessels, causing them to leak fluid or hemorrhage, ultimately leading to retinal damage. Over time, this can cause vision impairment or blindness if left untreated.

 

 Diabetic Nephropathy: Progression and Outcomes

The kidneys’ filtering units (glomeruli) become damaged due to prolonged high blood sugar levels. Protein leaks into the urine, and as the condition progresses, kidney function declines, often leading to end-stage renal disease.

 

 Diabetic Neuropathy: Types and Effects

 

 Peripheral Neuropathy

Peripheral neuropathy typically affects the feet and legs first, causing numbness, tingling, and pain.

 

 Autonomic Neuropathy

This form of neuropathy affects the autonomic nervous system, leading to issues such as gastroparesis (delayed stomach emptying), bladder problems, and blood pressure fluctuations.

 

 Cardiovascular Complications

Diabetes and heart disease are closely linked. High blood sugar damages the blood vessels and the nerves that control the heart. As a result, diabetic individuals are at a higher risk of heart attacks and strokes.

 

 Foot Complications in Diabetes

Diabetic foot complications are one of the most common reasons for hospital admissions among diabetic patients. Poor blood circulation and nerve damage can lead to foot ulcers, infections, and in severe cases, amputations.

Types of diabetes-related foot conditions

Individuals with diabetes face a heightened risk of infections or other complications stemming from any skin, nerve, or circulation problems in their feet. Conditions affecting the feet and toes that may result in complications include:

- Non-healing cuts, ulcers, burns, and blisters.

- Dry and cracked skin.

- Corns and calluses.

- Fungal infections, such as athlete’s foot and toenail fungus.

- Ingrown toenails.

- Hammertoes and bunions.

 

 Skin Complications Associated with Diabetes

People with diabetes are more susceptible to skin infections, such as bacterial and fungal infections. Diabetic dermopathy, a condition marked by brown patches on the skin, is also common.

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 Diabetes and its Impact on Mental Health

Living with diabetes can take a toll on mental health. Depression and anxiety are more prevalent in individuals with diabetes, affecting their ability to manage their condition effectively.

 

 Prevention and Management of Complications

The key to preventing complications in diabetes is maintaining tight glycemic control. This can be achieved through lifestyle interventions, including diet and exercise, medications, and regular monitoring of blood sugar levels.

 

 Advances in Treatment of Diabetes Complications

Recent advances in diabetes treatment include new medications that not only help control blood sugar but also protect against cardiovascular and kidney complications. Technological innovations like continuous glucose monitors (CGMs) and insulin pumps have also improved diabetes management.

 

 Challenges in Managing Complications

Despite these advances, challenges such as healthcare access, the cost of treatment, and patient adherence to therapy remain barriers to optimal management of diabetes complications.

 

 Conclusion

Complications associated with diabetes mellitus, both acute and chronic, significantly impact the lives of those affected. However, with proper management, many of these complications can be prevented or delayed. Early diagnosis, lifestyle changes, and advancements in treatment continue to play a critical role in improving outcomes for diabetic patients.

 

 FAQs

 What are the most common complications of diabetes?

The most common complications include diabetic retinopathy, nephropathy, neuropathy, and cardiovascular diseases.

 

 How can diabetic complications be prevented?

Complications can be prevented by maintaining proper blood sugar control, regular medical checkups, and following a healthy lifestyle.

 

 Is diabetic neuropathy reversible?

While diabetic neuropathy cannot be completely reversed, its progression can be slowed down with proper management.

 

 What is the link between diabetes and heart disease?

Diabetes increases the risk of heart disease due to damage to the blood vessels and nerves that control the heart.

 

 Can stress worsen diabetes complications?

Yes, stress can negatively impact blood sugar control, which may exacerbate complications in diabetic patients.

References :

1. Lvovs D, Favorova OO, Favorov AV. A Polygenic Approach to the Study 
of Polygenic Diseases. Acta Naturae. 2012 Jul;4(3):59-71. PMID: 23150804; PMCID: PMC3491892.

2. Eyth E, Naik R. Hemoglobin A1C. [Updated 2023 Mar 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549816/

3. Surwit RS, Schneider MS, Feinglos MN. Stress and diabetes mellitus. Diabetes Care. 1992 Oct;15(10):1413-22. doi: 10.2337/diacare.15.10.1413. PMID: 1425110.