Author: Siniša Franjić1*
Abstract
Diabetes presents a significant threat worldwide. Estimates indicate that around one in every eleven adults has this condition. It is important to consider the insights from the World Health Organization when talking about diabetes on a global level. In brief, the statistics are concerning.
Over 40% of individuals with diabetes are unaware they have it. Common signs of this illness include feeling very thirsty, needing to urinate often, fatigue, and having blurred vision.
Diabetes is a long-lasting metabolic condition marked by high blood sugar levels, which can cause severe damage to essential organs such as the heart, blood vessels, eyes, kidneys, and nerves over time. The most prevalent type is type 2 diabetes, primarily affecting adults, and arises when the body either resists insulin or cannot produce enough of it. In the last thirty years, the rate of type 2 diabetes has surged dramatically across countries of varying income levels. Meanwhile, type 1 diabetes, historically referred to as juvenile diabetes or insulin-dependent diabetes, is a chronic illness where the pancreas fails to produce sufficient insulin. For those living with this condition, having access to affordable treatments, particularly insulin, is vital for their survival.
Currently, about 830 million people globally are diagnosed with diabetes, with most residing in low- and middle-income countries. More than half of these individuals do not receive treatment. Both the total number of people with diabetes and those who are untreated have been on the rise over recent decades.
Keywords: Diabetes, Complications, Global Threat, Diagnosis, Health
Introduction
The metabolic disorder known as diabetes mellitus can lead to long-term complications that damage multiple organ systems over time [1]. Issues like neuropathy, retinopathy, nephropathy, and vascular dysfunction can develop even before clinical symptoms appear. This “silent damage” poses a significant threat to patients since early warning signs often go unrecognized, resulting in irreversible damage and a decrease in quality of life. Regular screenings, such as nerve conduction tests, retinal examinations, and renal function assessments, can help detect problems early and slow or stop their progression. It is also essential to teach individuals how to monitor their symptoms and collaborate with healthcare professionals to report them early. The number of people with diabetes continues to rise globally, particularly in middle- and low-income countries. Therefore, our approach should shift from merely treating the condition to proactively detecting and preventing diabetes. To stop the slow but steady advancement of diabetes-related complications, it is essential to be vigilant, consistently evaluate, and implement integrated healthcare methods. Recognizing and addressing early warning signs may lead to fewer complications, better outcomes for patients, and a reduction in the long-term socioeconomic impacts of diabetes-related disabilities.
Global Threat
Diabetes has emerged as a worldwide threat to people's health, posing significant risks to individuals across the globe [1]. According to a study from the International Diabetes Federation, the number of individuals aged 20 to 79 with diabetes is expected to jump from 537 million in 2021 to 783 million by 2045. The rise in diabetes cases is linked to urban growth, unhealthy lifestyles, and an increasing elderly population. This condition leads to various complications, including heart disease, kidney damage, strokes, nerve issues, heart attacks, and problems with blood vessels, all of which can severely affect health, finances, and social interactions. The World Health Organization (WHO) recognizes diabetes as a top cause of long-term disability and mortality. Alarmingly, estimates suggest that around half of those with diabetes are not diagnosed until their symptoms become critical. Many people overlook the long-term repercussions of diabetes, making it easier to disregard the disease's warning signs. Hyperglycemia’s severity often goes unacknowledged, as its effects don't show up as quickly as other illnesses.
Globally, diabetes affects 10.5% of adults, making it a serious public health challenge [2].
There are various types of diabetes, including type 1, which primarily affects children and teenagers, type 2, and less common forms like gestational diabetes and maturity-onset diabetes of the young. The ratio of type 1 to type 2 diabetes is roughly 1 to 9. Type 1 diabetes treatment relies heavily on insulin therapy and educating the patient and their family. For type 2 diabetes, the goal is to maintain glycated hemoglobin (Hb) A1C at or below 7% for most patients, focusing on four main strategies: hygiene practices, dietary recommendations, potential insulin use, and the patient's own blood sugar monitoring. Patient education plays a crucial role in managing this condition.
In addition to the essential insulin replacement for type 1 diabetes, the range of treatments available for type 2 diabetes has greatly expanded in recent years. Oral antidiabetic medications (OADs) may be used alone or in combination, affecting insulin sensitivity, stimulating beta cell activity, inhibiting alpha-glucosidase, and blocking sodium-glucose-linked transporter 2. The types of antidiabetic drugs include biguanides, sulfonylureas, glinides, alpha-glucosidases, and gliptins (which are diphosphodiesterase IV inhibitors). GLP-1 analogues are also available and are administered through subcutaneous injections. Moreover, continuous glucose monitoring devices have dramatically changed how glycemic control is achieved.
While allergies related to diabetes treatments are uncommon, allergologists and dermatologists may increasingly encounter these cases.
Extreme Consequences
Severe hypoglycemia and ketoacidosis are examples of the most serious outcomes of diabetes [1]. On the other hand, conditions like retinopathy, nephropathy, neuropathy, and cardiovascular disease represent the chronic complications that can affect multiple organ systems over time. The absence of widely accepted diagnostic standards makes it challenging to accurately gauge how often these complications arise. However, it is likely that most individuals with diabetes will experience one or more of these complications. In advanced stages, diabetes can lead to severe vision loss, kidney failure requiring dialysis or a transplant, heart attacks, strokes, and even amputations. The term "silent damage" refers to the gradual progression of diabetes-related issues that are not obvious and tend to go unnoticed until significant advancement has occurred. Yet, with proper lifelong management of diabetes and an emphasis on maintaining a healthy lifestyle, many of these severe or life-altering complications can potentially be prevented. The likelihood of experiencing complications is linked to the duration of diabetes and the quality of glycemic control achieved. A common approach to tracking this control over two to three months is through measuring glycated hemoglobin, or HbA1c. The risk for complications varies among those with diabetes; some individuals face challenges despite having lower HbA1c levels, which usually suggest good glycemic control.
Neuropathy, retinopathy, and nephropathy are three significant microvascular effects associated with diabetes. Data from cohort studies indicate that the prevalence of diabetic neuropathy in both adults and youths varies widely, from 2.4% to 75.1%. When other potential causes are ruled out, diabetic neuropathy can be defined as a diverse group of neurological disorders that negatively affect the peripheral nervous system. Diabetic peripheral neuropathy can be classified into four types: diffuse neuropathy, mononeuropathy, radiculopathy, and other neuropathies, each exhibiting different patterns, which may lead to either painful or painless symptoms. The most common type, diffuse neuropathy, impacts 75% to 90% of affected individuals. Those with diabetic peripheral neuropathy may face complications in the lower extremities, such as ulceration, infection, deformities, and amputations. Advancements in the diagnosis and treatment of diabetic peripheral neuropathy could result from research that clarifies the intricate pathogenesis involved. Early identification of diabetes-related issues is crucial to avoiding long-term disability. Symptoms often develop quietly over the years, becoming evident only after significant microvascular and macrovascular damage has occurred. Early detection not only reduces complication risks but also allows for more precise treatment strategies, such as optimizing blood pressure management, enhancing cholesterol control, or achieving tighter glycemic levels. Implementing lifestyle changes, like improving diet, increasing physical activity, and quitting smoking, has a higher chance of success when initiated before any major organ damage occurs.
Complications
The complications related to diabetes are quite intricate, while the disease itself is generally recognized [1]. In the early stages of type 2 diabetes (T2DM), high blood sugar levels lead to oxidative stress and a buildup of advanced glycation end products (AGEs). As the disease advances, oxidative stress may further damage respiratory chain components through protein glycation and mitochondrial DNA (mtDNA). Metabolic imbalances can trigger inflammation, which may then result in cell aging or death due to the binding of glycation products to receptors. These structural changes can contribute to various vascular issues linked to diabetes. Several new classes of medications, such as SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists, have been introduced in clinical settings to improve these conditions. However, early instances of high blood sugar can still lead to diabetes-related complications. For the phenomenon known as hyperglycemic memory, a fundamental driving force is required. The enduring changes at the cellular level indicate an organism's ability to revert to a prior metabolic state, which can play a significant role in the progression of diabetes and its long-term complications.
The primary mechanisms that explain the effects of diabetes include inflammation, immune response, oxidative stress, mitochondrial dysfunction, aging, and various types of cell death. Factors such as noncoding RNAs (ncRNAs), DNA methylation, and histone modifications can influence the development of a heritable phenotype without changing DNA sequences. These epigenetic changes govern the physiological and pathological processes associated with metabolic memory and the impact of diabetes.
In acute situations, high blood sugar may signal an acute infection [3]. Nonetheless, it is standard practice to check an HbA1c level upon arrival and assess blood glucose monitoring tools to understand recent diabetes management trends. This has become much easier with the availability of flash and continuous glucose monitors that can either be bought or funded by health services. It's essential to rule out diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS) for any patient presenting with hyperglycemia, as these conditions require urgent treatment along with stabilization in cases of an active foot ulcer.
Patients may develop severe life-threatening complications from diabetes, such as serious sepsis due to an infected diabetic foot. For DKA, a continuous insulin infusion is recommended, along with prompt fluid replacement to address the osmolar implications of high blood sugar and to enhance circulation.
Treating DKA requires preparing 50 units of Actrapid insulin mixed in 50 mL of 0.9% saline solution, which should be given hourly depending on the patient's weight. Once DKA or HHS has been managed, the patient can transition to either a variable rate insulin system or subcutaneous insulin therapy. When opting for the variable rate infusion, the insulin dosage is determined either by the requirement for DKA recovery or the patient's usual insulin intake. It's crucial to watch for low blood sugar (hypoglycaemia) throughout the treatment process. There should be a clear plan for addressing hypoglycaemia in patients receiving insulin infusions.
Maintaining stable glucose levels during both the acute and recovery stages supports immune function and enhances the healing of wounds.
Vascular Complications
Individuals with diabetes mellitus and accompanying microvascular complications seem to face a heightened risk of accelerated atherosclerosis, which can result in cardiovascular and cerebrovascular events, as well as increased early mortality [1]. Microvessels, which include arterioles, capillaries, and venules, serve as the basic functional component of the cardiovascular system. Their structure and cellular characteristics differ from those of macrovessels. While macrovessels primarily supply blood to organs, microvessels are essential for delivering nutrients properly and regulating blood pressure. Regulatory mechanisms influence vascular permeability and myogenic responses, allowing microcirculation to adapt blood flow based on specific metabolic needs. Before clear signs of hyperglycemia and vascular damage appear, some dysfunction in microvascular activity may already exist. The term diabetic microangiopathy describes the condition where the microvasculature undergoes specific pathological changes. These alterations, such as thickening of the capillary basement membrane, affect arterioles in areas like the retina, heart, skin, and muscle. This thickening can lead to various clinical issues, including hypertension, slow wound healing, and tissue hypoxia, ultimately causing irregular vascular function. Neovascularization from the vasa vasorum may also indicate potential platelet rupture, promote atherosclerosis, and connect macro- and microangiopathy. The link between microvascular disease and the development of macrovascular atherosclerosis and other systemic effects of diabetes is still not fully understood.
Early Detection
Hyperglycemia is the defining characteristic of T2DM, a metabolic condition that evolves over time [1]. Various issues, such as cardiovascular disease, renal problems, and retinopathy, can arise from consistently elevated blood glucose levels. Failing to diagnose diabetes promptly can worsen many health challenges. Extended periods of high blood sugar can lead to complications affecting the cardiovascular system, kidneys, nervous system, and eyes. Since early stages of diabetes often show no clear symptoms, it can easily go undetected. Untreated high blood sugar can harm blood vessels and the nervous system, leading to further complications. Therefore, early diagnosis and treatment can effectively reduce these risks. Besides recognized risk factors, alternative methods can help identify individuals at risk for T2DM. Three additional approaches for diagnosing prediabetes include the following.
Glycated albumin (GA) is a new biomarker designed to assist those with diabetes in monitoring their blood sugar levels over shorter durations. Similar to HbA1c, GA reflects average glucose levels over a period of 2–3 weeks and is useful for diabetes management. Its increased sensitivity and specificity have improved early diagnosis and treatment of diabetes. When assessing African prediabetics, using GA alongside HbA1c detected nearly 80% compared to just HbA1c alone (78% versus 50%, P < 0.001). A GA level of ≥17.1% can identify most undiagnosed diabetes cases during fasting glucose testing. The use of GA reduced false-positive screening results by 33.75%, compared to fasting glucose measures. Particularly in high-risk groups, especially those exhibiting normal fasting glucose, an abnormal GA level serves as an important marker for OGTT screening.
Continuous glucose monitoring (CGM) serves as an innovative approach to tracking changes in patients' glucose levels, including their after-meal spikes, in real-time. There are numerous advantages to utilizing CGM over traditional glucose monitoring methods like frequent blood tests or fingerstick checks. First, CGM provides a continuous recording of a patient’s glucose levels throughout the day. This allows for a better understanding of glycemic variability, enabling the identification of more accurate trends or patterns compared to intermittent testing. Furthermore, continuous glucose monitors can recognize fluctuations in blood sugar levels triggered by different factors, such as food intake, exercise, emotional stress, and medications. This information is vital for healthcare providers and patients to develop customized treatment strategies and make informed choices regarding diet, physical activity, and medication adjustments. Clinical glucose monitors show potential as valuable tools for diagnosing and treating individuals who are prediabetic and other high-risk groups prone to developing diabetes. Those who wore continuous monitoring devices for a minimum of 24 hours demonstrated impaired glucose tolerance if their fasting blood glucose was under 100 mg/dL. By supplying ongoing blood glucose data, incorporating CGM into routine clinical practice enhances care for prediabetes. Recent technological improvements in continuous glucose monitoring, such as advanced sensors and smaller devices, have led to more dependable and user-friendly options. The rise in popularity of CGM can be attributed to patients' increasing interest in better blood glucose control and overall health. However, challenges exist, particularly its high cost, which limits its accessibility to certain populations and regions.
Diagnosis
Diabetic neuropathies consist of a wide range of disorders with varying clinical symptoms [4]. Notably, around 50% of individuals may have diabetic neuropathy without showing any clear signs. As a result, timely and accurate diagnosis, along with a thorough evaluation, is crucial for managing peripheral neuropathy effectively in older diabetes patients.
The American Diabetes Association and the International Working Group on the Diabetic Foot advise regularly screening individuals with diabetes for neuropathy and loss of protective sensation using basic tests to identify those at higher risk for diabetic foot ulcers. This involves a careful review of the patient's medical history and tests to assess both small and large-fiber function, which can be evaluated through temperature or pinprick sensations, a 128-Hz tuning fork, and 10-g monofilament testing to pinpoint at-risk individuals. Following these guidelines, those diagnosed with diabetes should be evaluated for peripheral neuropathy immediately upon diagnosis in T2DM and five years after diagnosis in T1DM. Additionally, ongoing evaluations, at least annually, are essential thereafter.
The current methods in clinical practice often overlook the initial signs of neuropathy, highlighting the need for prompt treatment to prevent further progression. It's essential to close this gap by developing a clear and accurate test or a series of tests that can identify and diagnose diabetic neuropathy at its early stages. This strategy will help reduce the chances of foot ulcers and lower the risk of amputations. This is particularly important for the growing number of older adults with diabetes, especially since the rates of diabetes have been rising in this group.
Obesity
Obesity is widely recognized as a significant risk factor for developing type 2 diabetes. Reports suggest that 60–90% of type 2 diabetes cases are directly linked to obesity [5]. Gaining weight, especially around the abdomen, leads to insulin resistance. To keep blood sugar levels stable, the pancreas's beta cells must produce more insulin (hyperinsulinaemia), which can eventually cause damage to beta-cell function and could ultimately lead to their failure.
Obesity stands out as the primary risk factor for developing type 2 diabetes, playing a crucial role in the rising global rates of the disease. The combination of obesity and diabetes has introduced the term ‘diabesity’, which carries significant treatment implications. Obesity results from consuming more energy than one’s daily energy needs, leading to surplus energy being stored as fat in the body, both under the skin and around internal organs.
To assess obesity, one common method is to calculate a person's body mass index (BMI), which involves dividing weight in kilograms by height in metres squared. The resulting BMI value is used to categorize obesity according to World Health Organization (WHO) standards. However, BMI does not consider a person's body composition, such as the proportion of visceral fat, subcutaneous fat, and muscle. This is crucial for evaluating obesity. For example, individuals with high muscle mass, like athletes or rugby players, may be classified as obese based on their BMI. Including waist circumference along with BMI can provide a more accurate assessment of an individual’s obesity risk.
Obesity is theoretically defined as the excess health risks associated with body fat exceeding what is typically seen in the population [6]. For practical purposes, the World Health Organization (WHO) sets the definition of obesity in adults as a body mass index (weight in kg divided by height in meters squared) of 30 or higher. The WHO views the rapid rise in obesity rates across all ages, especially since the 1970s, as a global obesity epidemic. Currently, around 650 million adults and about 340 million children and teenagers aged 5 to 19 are affected by obesity. Obesity tends to be more common among women and older individuals than in men and younger groups. Although food availability is crucial, our understanding of the causes of obesity is still quite limited. Studies indicate that obesity can "run in families," where both genetic factors and environmental influences, particularly social ones, are significant. This condition is linked to increased risks of various medical, mental, and social issues, notably a strong connection to type 2 diabetes. Type 2 diabetes, along with metabolic syndrome and related diseases, plays a major role in the higher rate of illness and death associated with obesity.
Diabetes mellitus ranks among the most prevalent endocrine disorders in children [7]. It is a chronic condition that impacts not only the children but also their families' health. While type 1 diabetes mellitus (T1D) is still the predominant form of diabetes in children, the rise in childhood obesity has led to a growing incidence of type 2 diabetes mellitus (T2D). Advancements in human genetics have also led to the identification and characterization of monogenic types of diabetes. Despite the progress made with insulin and diabetes technology, effectively managing diabetes mellitus hinges on teamwork between patients and healthcare providers to maintain a high quality of life and prevent long-lasting complications. Because children have unique developmental and physiological needs, their care standards must differ from those designed for adults.
Prevention
The main goal of preventing and managing complications from diabetes is to lower morbidity and mortality rates while improving quality of life [8]. There is also significant attention on minimizing the financial strain diabetes creates. This includes not just direct medical costs but also indirect costs like decreased productivity, which impact both those living with diabetes and their families. The repercussions of diabetes extend beyond individual finances, putting pressure on local, national, and global resources. By implementing effective management and preventive strategies, we can achieve better health outcomes for patients and ultimately save money and optimize resources at various levels.
Effectively controlling diabetes is essential for reducing the chances of complications. Keeping blood glucose levels in check can cut the risk of developing eye, kidney, and nerve diseases by as much as 40%. It’s also important to manage blood pressure, which can lower the likelihood of heart disease and stroke by around 33% to 50%. Additionally, maintaining healthy cholesterol levels can result in a 20% to 50% decrease in cardiovascular issues.
It's crucial to have regular eye check-ups and timely treatments, as these can prevent nearly 90% of diabetes-related blindness. Healthcare services focused on routine foot assessments and educating patients can also significantly help in avoiding up to 85% of diabetes-related amputations.
Furthermore, catching diabetic kidney disease early and using kidney-protective medications to manage blood pressure can slow kidney function decline by 33% to 37%. These figures highlight how vital thorough diabetes management is for the health and safety of individuals living with this condition.
In terms of preventing complications from diabetes, digital tools and devices have made a significant impact. These innovations play an important role in every aspect of managing and preventing diabetes.
Conclusion
Diabetes is a condition that affects metabolism and is defined by high blood sugar levels, resistance to insulin, and insufficient insulin production. Long-term issues that arise from high blood sugar can lead to serious health problems, including heart disease, stroke, diabetic eye disease, kidney failure, and poor blood flow in the limbs, which might result in amputation. Those who have diabetes face double the risk of dying from heart-related illnesses or strokes compared to individuals without the disorder. This disease has become a worldwide concern, with the number of people affected reaching alarming figures that were hard to imagine just a few decades ago. Multiple factors contribute to this increase, with the most significant being changes in lifestyle, such as eating more high-calorie foods and exercising less. These issues emphasize how serious diabetes has become in our modern society. Specifically, lifestyle choices like decreased physical activity and the easy access to high-calorie fast food raise the likelihood of developing diabetes and its related health problems. Additionally, the complications linked to diabetes create a heavy financial strain on healthcare systems globally, making it vital to emphasize prevention strategies to avoid these serious health issues.
References
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Citation: Franjić, S. (2026). Diabetes is Major Global Health Threat. J. Diabetes Endocr. Educ. Res.