Retha Harmse explores how fibre influences blood glucose, its benefits for people with diabetes, and practical tips for integrating fibre-rich foods into everyday meals.

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Understanding fibre

Fibre, found in plant-based foods, comes in two main types: soluble and insoluble.

Soluble fibre

• Soluble fibre dissolves in water to form a gel-like substance in the digestive tract.
• This type of fibre is known for its ability to absorb water, slow down digestion, and help regulate blood glucose levels.
• Common sources include oats, barley, legumes (beans and lentils), fruits (apples, oranges, and berries), and some vegetables (Brussels sprouts and carrots).

Insoluble fibre

• Insoluble fibre doesn’t dissolve in water and remains relatively unchanged as it passes through the digestive system.
• It adds bulk to stools and promotes regular bowel movements, aiding in the prevention of constipation and supporting overall gut health.
• Foods rich in insoluble fibre include whole grains (wheat, brown rice, and quinoa), nuts, seeds, vegetables (broccoli, cauliflower, and dark leafy greens), and the skins of fruits.

Both types of fibre are essential for optimal health and should be included in a balanced diet. While soluble fibre primarily influences blood glucose regulation, insoluble fibre contributes to digestive health and bowel regularity.

Fibre’s impact on blood glucose

Understanding the intricate relationship between fibre intake and blood glucose levels is essential for effective diabetes management. Fibre influences blood glucose levels through various mechanisms, primarily attributed to its impact on digestion, carbohydrate absorption, and satiety.

1. Mechanism of action

• Fibre-rich foods, particularly those containing soluble fibre, alter the digestion and absorption of carbohydrates in the gastrointestinal tract.
• Unlike simple carbohydrates that are rapidly broken down into glucose and absorbed into the bloodstream, fibre slows down this process, resulting in a gradual and steady release of glucose into the bloodstream.

2. Soluble fibre’s role in blood glucose regulation

• Soluble fibre forms a gel-like substance when combined with water in the digestive tract.
• This gel slows down the digestion of carbohydrates, leading to a slower release of glucose into the bloodstream.
• Consequently, soluble fibre helps prevent rapid spikes in blood glucose levels after meals, promoting more stable and controlled glycaemic responses.
• Foods high in soluble fibre (oats, legumes, and certain fruits) are particularly beneficial for people with diabetes in managing postprandial glucose levels.

3. Impact of insoluble fibre on satiety and carbohydrate intake

• Insoluble fibre adds bulk to the diet and promotes feelings of fullness and satiety, which can help regulate appetite and reduce overall food intake.
• By increasing satiety, insoluble fibre may indirectly influence blood glucose levels by moderating carbohydrate consumption.
• Additionally, insoluble fibre contributes to digestive health and regular bowel movements, which are crucial for overall well-being.

Benefits for people with diabetes

Fibre-rich foods offer numerous advantages for people with diabetes, playing a critical role in managing blood glucose levels, enhancing insulin sensitivity, and supporting weight management.

Understanding these benefits can empower you to make informed dietary choices and optimise your diabetes management strategies.

1. Regulation of blood sugar levels

• One of the primary benefits of fibre is its ability to regulate blood glucose levels, particularly after meals.
• By slowing down the digestion and absorption of carbohydrates, soluble fibre helps prevent rapid spikes in blood glucose levels following meals.
• This controlled release of glucose into the bloodstream supports more stable and consistent glycaemic responses, reducing the risk of hyperglycaemia and its associated complications.

2. Improved insulin sensitivity

• Research has shown that fibre intake may enhance insulin sensitivity, a key factor in diabetes management.
• Insulin sensitivity refers to the body’s ability to respond effectively to insulin, the hormone responsible for regulating blood glucose levels.
• Fibre-rich diets have been associated with improved insulin sensitivity, potentially reducing the body’s reliance on exogenous insulin or other diabetes medications.
• By promoting better insulin sensitivity, fibre can help you achieve better glycaemic control and reduce your risk of insulin resistance-related complications.

3. Management of weight

• Weight management is a crucial aspect of diabetes control, as excess body weight can exacerbate insulin resistance and increase the risk of complications.
• Fibre-rich foods, particularly those high in insoluble fibre, contribute to feelings of fullness and satiety, which can help control appetite and reduce overall calorie intake.
• Additionally, fibre-rich diets are often lower in energy density and higher in nutrient density, making them conducive to weight management and overall health.
• By promoting satiety and reducing kilojoule intake, fibre-rich foods can support weight loss or weight maintenance goals, which is essential for optimal diabetes control and prevention of related complications.

Recommended intake and practical tips

The American Diabetes Association recommends daily fibre intake of 25 grams for women and 38 grams for men. Achieving this goal involves incorporating fibre-rich foods like whole grains, fruits, vegetables, legumes, nuts, and seeds into meals and snacks.

Practical tips for increasing fibre intake

• Incorporate fibre-rich foods into meals and snacks. Choose whole grains, fruits, vegetables, legumes, nuts, and seeds as primary sources of dietary fibre. Aim to include a variety of these foods in your daily meals to ensure adequate fibre intake.
• Start the day with a fibre-rich breakfast. Opt for whole grain cereals, oatmeal, or smoothies with added fruits and vegetables to kickstart your day with a fibre boost.
• Choose whole grains over refined grains. Replace refined grains with whole grains (brown rice, quinoa, barley, and whole wheat bread) to increase your fibre intake while also benefiting from additional nutrients.
• Snack on fibre-rich options. Keep snacks like fresh fruits, raw vegetables, nuts, and seeds on hand for convenient and nutritious fibre-rich snacking options.
• Experiment with plant-based meals. Incorporate meatless meals centred around beans, lentils, tofu, or other plant-based proteins to increase your fibre intake while also reducing saturated fat and cholesterol intake.
• Read food labels. Pay attention to food labels and choose products that are high in fibre. Look for whole grain products with at least 6 grams of fibre per 100g.

Best fibre-rich foods for people with diabetes

Whole grains, fruits, vegetables, legumes, nuts, and seeds are excellent sources of fibre. Incorporating these foods into daily meals and snacks can help meet fibre intake goals and support blood glucose management.

Incorporation tips

• Substitute refined grains with whole grain options in meals such as sandwiches, wraps, salads, and side dishes.
• Enjoy fruits as snacks, add them to breakfast cereals, yoghurt, or smoothies, or incorporate them into salads and desserts.
• Include vegetables in meals and snacks by adding them to soups, stir-fries, salads, omelettes, or enjoying them as raw veggie sticks with hummus or yoghurt dip.
• Use legumes as the main ingredient in soups, stews, chilli, salads, or veggie burgers, or enjoy them as a side dish or snack.
• Add nuts and seeds to oatmeal, yoghurt, salads, or smoothies, or enjoy them as a standalone snack.

Meal planning tips

Meal planning is crucial for optimising fibre intake and managing diabetes effectively. Sample meal plans featuring fibre-rich foods are outlined, along with strategies for making healthier food choices. Tips include choosing whole grains, loading up on vegetables, including legumes, snacking wisely, reading labels, and staying hydrated.

1. Choose whole grains: Opt for whole grain varieties of bread, pasta, rice, and cereal to increase fibre intake and promote satiety.
2. Load up on vegetables: Incorporate a variety of colourful vegetables into meals and snacks to boost fibre content and add essential nutrients.
3. Include legumes: Add beans, lentils, and chickpeas to soups, salads, and main dishes for a hearty dose of fibre, protein, and minerals.
4. Snack wisely: Choose fibre-rich snacks such as fresh fruit, raw vegetables with hummus, Greek yoghurt with nuts and seeds, or whole grain crackers with cheese.
5. Read labels: Check food labels for fibre content and choose products with higher fibre content per serving.
6. Hydrate: Drink plenty of water throughout the day to support digestive health and aid in the movement of fibre through the digestive tract.

Precautions and considerations

While increasing fibre intake offers numerous health benefits, precautions should be taken, especially if you have diabetes. Gradually increasing fibre intake, monitoring for gastrointestinal side effects, discussing fibre supplements with healthcare providers, monitoring blood glucose levels, and adopting an individualized approach are essential considerations.

Fibre for the win

Fibre plays a crucial role in managing blood glucose levels in people with diabetes. By understanding the impact of fibre on blood glucose, incorporating fibre-rich foods into the diet, and following practical tips for meal planning, you can take control of your diabetes and improve your overall health and well-being.

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Dr Marius Wasserfall looks at semaglutide, the so-called wonder drug for weight loss and, more importantly, the safety for those without diabetes.

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As more South Africans turn to medical interventions for weight loss, semaglutide (originally developed as a treatment for Type 2 diabetes) has gained rapid recognition.

Semaglutide can be a valuable adjunct to lifestyle changes like diet and exercise. Though it’s not a silver bullet but can help patients battling obesity make real progress when combined with healthy habits.

Obesity is a growing concern worldwide, with predictions indicating that by 2030, half of the world’s population will be overweight or obese. In South Africa, this figure has already been reached, with more than 50% of adults classified as overweight or obese.

The challenge with obesity is complex. It involves not just will power, but changes in the brain’s appetite regulation and metabolic processes that make long-term weight loss difficult.

Semaglutide works by addressing this challenge at the root. It affects hunger and satiety hormones in the brain, helping people feel fuller for longer and reducing their appetite.

Glucagon-like peptide-1 receptor agonists

Semaglutide, which belongs to a class of drugs called Glucagon-like peptide-1 (GLP-1) receptor agonists, was only officially approved for treating Type 2 diabetes in 2017.

During clinical trials, however, a secondary effect became apparent during clinical trials: patients were experiencing significant weight loss. This discovery has led to semaglutide being prescribed off-label for weight management, although it’s not approved by the South African Health Products Regulatory Authority (SAHPRA) for this purpose. It remains a scheduled product and can only be sold by a pharmacy with a valid prescription from a doctor.

In 2021, the US Food and Drug Administration (FDA) approved a higher dose of semaglutide, specifically for chronic weight management in individuals with obesity or related health conditions. Since then, demand for semaglutide has skyrocketed, driven by glowing endorsements from celebrities and widespread attention on social media platforms.

Risks associated with non-approved purposes

While studies show that semaglutide users may experience up to 15% weight loss, experts warn of potential risks when it is used without medical supervision or non-approved purposes.

Side effects can include nausea, vomiting, and diarrhoea, and long-term safety for non-diabetic users remains unclear. While serious adverse effects are very seldom seen, they include acute pancreas inflammation and gallbladder problems. Some studies involving rodents found that this medication resulted in medullary cancer of the thyroid.

Counterfeit products

Additionally, there are growing concerns about counterfeit semaglutide entering the market. The high demand for the drug, especially for its off-label use, has exceeded forecasts and created opportunities for illegal manufacturers to supply counterfeit products.

When you purchase from an unlicensed manufacturer, there’s no quality assurance. The product may not contain the active ingredient or, worse, it may include harmful substances. Both the FDA and SAHPRA have issued warnings about the dangers of counterfeit versions of these medications.

Despite its effectiveness, there are also concerns about the long-term sustainability of weight loss achieved through semaglutide. Stopping the medication will likely result in the majority of the weight being regained. Studies back this up, showing that patients tend to regain most of the weight after discontinuing semaglutide or similar GLP-1 receptor agonists.

The reason for this lies in how these medications work. Semaglutide improves the brain’s regulation of appetite and alter the body’s biology. However, once you stop using it, your brain biology reverts to its previous state, and you will likely regain the weight.

Cost implications

Affordability is therefore a major factor. These medications are expensive, and many medical schemes will not cover them for weight management, only for diabetes.

This makes it essential for people considering semaglutide or similar drugs to weigh the costs carefully and recognise the commitment required to maintain results.

Availability is another concern. As demand grows among those seeking weight loss, shortage of the drug is making it difficult for people with diabetes, who rely on semaglutide to manage their condition, to access the medication. This has led to calls for caution and more stringent regulations to ensure the drug remains accessible for those who need it most.

Broader societal issue

Semaglutide’s popularity as a quick-fix weight loss solution highlights a broader societal issue: the pressure to conform to ideal body standards. Healthcare professionals stress that any weight-loss treatment should be approached with caution and always in consultation with a medical professional.

Medications like semaglutide are just one piece of the puzzle and weight management remains a multi-faceted issue that requires long-term lifestyle changes to achieve and maintain results.

While GLP-1 receptor agonists show promising results for weight loss, the focus should shift to prevention. We need to prioritise preventing obesity, especially in our youth, to reduce our reliance on costly, lifelong medications like semaglutide. Encouraging healthy habits is crucial. Ultimately, it comes down to this: you’ll face either the pain of self-discipline or the pain of regret; the choice is yours.

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Dr Angela Murphy looks at how Type 2 diabetes remission can be achieved and how anyone living with Type 2 diabetes can aim for this.

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Receiving a diagnosis of Type 2 diabetes can be distressing. It is a chronic condition that truly invades into daily life. The aim is to keep it controlled to prevent and avoid any future complications. Could you do even better than control? Could you, in fact, reverse Type 2 diabetes?

To achieve diabetes remission, or reversal, certain criteria need to be met. According to the American Diabetes Association these criteria are:

Full diabetes remission – Fasting blood glucose (FBG) < 5.56mmol/L and HbA1c < 6.0% on no diabetes treatment.

Partial diabetes remission – FBG is 5.56-6.9mmol/L and HbA1c 6.0 -6.5% on no diabetes treatment.

Classification of Type 2 diabetes

New research has suggested that there may be four subtypes of Type 2 diabetes. This is important to be aware of as it will influence attempts to reverse diabetes.

1. Severe insulin-deficient diabetes (SIDD) – Diagnosed at a younger age, lower body mass index (BMI), and early need for insulin therapy.
2. Severe insulin-resistant diabetes (SIRD) – Higher BMI and features of insulin resistance.
3. Mild obesity-related diabetes (MOD) – Younger age at diagnosis with high BMI and moderate insulin resistance
4. Mild age-related diabetes (MARD) – Older age with ‘mild’ diabetes in that very little medication is used to control glucose levels.

Interventions

Currently, interventions to achieve diabetes reversal are aimed at weight loss and kilojoule restriction. These interventions are not appropriate for the MARD person who may develop significant muscle loss and worsen overall health. The intervention may not be adequate for the SIDD who even with weight loss doesn’t have enough endogenous insulin production. However, most people with Type 2 diabetes are overweight or obese and will benefit. The accepted interventions are:

1. Dietary

In 2011, the Counterpoint Study showed that extreme kilojoule restriction could normalise blood glucose levels in a group of people with Type 2 diabetes. The 11 study volunteers were given a liquid shake (Optifast – available in South Africa) and non-starchy vegetables totalling 2510,4kJ per day.

After the first week blood glucose levels dropped on average from 9.2mmol/L to 5.9mmol/L and remained there for the duration of the eight-week study. All diabetes medications were stopped. There was a significant improvement in insulin sensitivity in the liver and pancreas. This meant that the production of glucose in the liver decreased, and the pancreatic beta-cells could do their work again to control blood glucose. The average weight loss to achieve these changes was 15% of initial body weight.

The Counterbalance Study published in 2016 showed similar results in a larger group of patients with Type 2 diabetes who achieved normal blood glucose values for up to six months.

The DiRECT Trial, conducted in a general practice setting in the United Kingdom, showed diabetes remission in 46% of patients after a year and 36% of patients were still in remission after two years.  This showed that a kilojoule-controlled diet could induce diabetes remission.

There is similar evidence for the use of a low carbohydrate diet as a dietary intervention to induce diabetes remission. There is still some debate whether it’s the low carbohydrate intake per se or the associated overall drop in total kilojoules that produces the benefit. In my experience, I like patients to follow diets they prefer as reducing kilojoules is always hard work.

2. Surgery

Bariatric surgery has been used to treat obesity for many years. The sleeve gastrectomy, Roux-en-Y-gastric bypass, and biliopancreatic diversion are the three main procedures.

The Swedish Obese Subject study followed several hundred patients with Type 2 diabetes who underwent bariatric surgery for over two decades. At the end of the second year 72.3% of patients were in remission. This number decreased to 30.4% at 15 years post-surgery which is still significant.

We now talk about metabolic surgery which is defined as gastrointestinal surgery with the intent of treating diabetes and obesity. The improvement in glucose control post bariatric surgery occurs within days so it’s not entirely dependent on actual weight loss. The significant drop in kilojoules decreases the fat in the liver and pancreas, restoring normal function in these organs.

In addition, the levels of the gut hormone glucagon like peptide 1 (GLP-1) increase. These changes lower insulin resistance and increase insulin production which decreases blood glucose. Many medical and scientific societies now endorse bariatric surgery as an effective treatment for Type 2 diabetes and a means to achieve diabetes remission.

Factors that predict diabetes remission include:

• Age: Younger is more likely to experience remission.
• Duration of diabetes: A shorter history of diabetes is more likely to experience remission.
• Weight loss: Losing 10% or more of body weight in the year after diagnosis is a strong predictor of remission.
• Baseline glucose control: A lower HbA1c at time when weight loss is started is a predictor of remission.
• Baseline BMI: Higher baseline BMI is a predictor of remission.
• Baseline medications: Less medications, particularly insulin, at baseline is a predictor of remission.
• Triglyceride and gamma-glutamyl transferase levels (liver function tests): Lower baseline levels of these are predictors of remission.
• Quality of life: Reporting better quality of life with less anxiety or depression is a predictor of remission.

Takeaway message

Not all people given a diagnosis of Type 2 diabetes will be able to achieve diabetes remission. This may be due to the subtype of diabetes or the difficulty succeeding with extreme dietary changes, significant weight loss, or access to bariatric surgery.

For some people with Type 2 diabetes aiming for remission is a realistic goal and they should be given the information and access to care they need to achieve this.

Bariatric surgery offers an excellent chance of diabetes reversal, but it’s expensive, and it requires specialised units not necessarily available in every area. Lifestyle intervention should be a simpler option, but the kilojoule restriction is significant and for many people difficult to sustain. This is where newer medications, such as the GLP-1 receptor agonists (liraglutide, dulaglutide, and semaglutide) and the soon to be available, dual action tirzepatide, may help in the long-term use of very low-kilojoule diets.

However, if weight is successfully lost and normal glucose levels achieved while using these medications, we can’t call this diabetes remission. For the exact diagnosis of remission, no medications can be used.

It’s realistic for some people with diabetes to aim for remission. However, it’s extremely beneficial also to aim for good diabetes control which then decreases the risk of diabetes complications.

It’s much more beneficial to achieve a low HbA1c with diabetic medications than fail at attempts to reverse diabetes and end up with poor control. To achieve diabetes remission is possible but not easy. To achieve diabetes control is possible and usually easier.

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Dr Louise Johnson explains the dangers of deep vein thrombosis (DVT) and advocates prevention is better than cure.

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DVT is a blood clot in a vein, usually in the leg and is a type of peripheral venous disease (PVD).

The earliest known reference to PVD (the broad term referring to disorders affecting the blood vessels carrying blood to and from the arms and legs) is found on the Eber Papyrus, which dates from 1550 BC.

In more detail, DVT is the presence of coagulated blood, a thrombus, in one of the deep venous conduits that returns blood to the heart. DVT is defined as the development of a thrombus within the deep veins of the pelvis or lower limbs.

The prevalence of DVT is reported to be 100 per 100 000 people per year.¹ The incidence increase with age and the incidence is higher in men than in women.

Anatomy

The peripheral venous system functions both as a reservoir to hold extra blood and as a conduit to return blood from the periphery to the heart and lungs. Unlike arteries which possess three well-defined layers (a thin intima, a well-developed muscular media, and a fibrous adventitia), most veins are composed of a single tissue layer called endothelium. The lower limb deep venous system is typically thought of as two separate systems, one below the knee and one above.

Pathophysiology

In the 19^th century, Rudolf Virchow described three factors that are critically important in the development of DVT.

1. Venous stasis or sluggish blood flow
2. Activation of blood coagulation
3. Venous endothelial damage (vessel wall damage)

These factors have come to be known as the Virchow triad.

Risk factors

• Age – The incidence of DVT increases with age and is very rare in childhood.
• Orthopaedic surgery – DVT is more common in patients with lower limb fractures or after hip or knee replacement surgery.²
• Trauma – Incidence of DVT is significantly higher in patients with lower extremity fractures than those with trauma at other sites. The homeostasis of coagulation shifts to a pro-thrombotic state early after trauma injury. Thus, it is necessary to give anti coagulation medicine early on in treatment. Patients with trauma have a six-fold increase in DVT.
• Cancer
• Other factors, such as:
  • Immobility (flights or trips sitting longer than six hours)
  • Pregnancy and postpartum
  • Varicose veins
  • Heart attacks
  • Renal impairment
  • Long hospitalisation
  • Obesity
  • Hormonal therapy

Clinical manifestations

History

Patients will complain about local pain and swelling in a limb. Usually, it’s only on one side. Tenderness occurs in 75% of patients. Associated risk factors may be present.

Clinical picture

• Limb swelling
• Homans sign (Calf pain when the foot is flexed upwards. It is only seen in 50% of all DVT patients).
• The lower limb may have a red purple colour due to venous obstruction.
• A palpable, indurated, cordlike, tender subcutaneous venous segment.

Diagnosis

The American Academy of Family Physicians (AAFP) recommend a workup of patients with a probable DVT using the Wells scoring system. A Wells score of more than two has a high probability of a DVT.

Wells scoring system

Active cancer within six months +1

Immobilisation of lower limb in cast +1

Localised tenderness of venous system +1

Unilateral swelling of leg +1

Calf swelling more than 3cm circumferential increase+1

Previous DVT +1

Recent bedridden >3 days or major surgery +1

Alternative diagnosis at least as likely as DVT -2

Tests

D-dimer is a test that is easily performed by a blood sample. D- dimer is a small protein present in blood after a clot is degraded. Serum levels of D-dimer may increase in clinical conditions where clots form, for instance surgery, trauma, cancer, sepsis and haemorrhage, particularly in hospitalised patients. Interestingly, these conditions are also correlated with greater risk of DVT.³

The level of D-dimer remains increased in patients with DVT for approximately seven days. Patients that present late in the disease course may have a low level. Solitary DVT in the calf with a low clot burden may have a low D-dimer. Although D-dimer can’t verify DVT diagnosis, it may be highly useful to rule out DVT.

Venous ultrasound is the primary imaging modality to diagnose DVT. It’s safe, non-invasive, and cheap. The sensitivity of compression ultrasound in diagnosing DVT is 94% and its specificity is 98%.

Differential diagnosis

Other conditions that can cause similar symptoms as a DVT that should be considered are:

• Lymph node enlargement
• Superficial hematomas
• Femoral artery aneurism
• Baker’s cyst
• Superficial thrombophlebitis

Treatment

Left untreated, DVT can be complicated with pulmonary embolism (PE), which is a blockage in an artery of the lungs caused by a blood clot that has travelled from elsewhere in the body, at an early stage, and is associated with a high risk of recurrence.

Medical treatment

Low molecular weight heparin (LMWH) is recommended as an injection early in the diagnosis to stabilise the clot and prevent propagation of the clot and complications, such as pulmonary clots

Once intense anticoagulation is in place, the patient can be switched to either warfarin or to the newer drugs called non-vitamin K oral anticoagulants (NOACs). These drugs have less bleeding and is as effective as warfarin and need not be tested for dosing. Unfortunately, they are currently still expensive. There are three currently available in South Africa.

Other options

In patients with life-threatening clots, an inferior vena cava (IVC) filter can be inserted by a vascular surgeon.

In patients with massive iliofemoral thrombosis or limb-threatening thrombosis, thrombolysis (a procedure that breaks up blood clots using medication or a minimally invasive procedure) can be used. It has a risk of intracranial haemorrhage.

Prevention

The most important treatment of DVT is to always remember to take precautions to prevent it in the circumstances in which it may occur.

All patients admitted to hospital must be evaluated as a possible risk for a DVT.

Circumstances to consider

1. Choose anaesthesia well. Spinal or epidural anaesthesia can enhance blood flow and reduce DVT by approximately 50%.
2. Surgical technique. Meticulous operative skill with as little torsion of veins as possible to prevent endothelial vein damage. Choose surgeon wisely.
3. This should be adopted as soon as possible after operation. Walking improves the blood flow of the veins. Remember bedrest is exercise for the coffin.
4. Compression stockings. The below knee and above knee stockings have a similar effect if the stockings are well-fitted.
5. Intermittent pneumatic compression. This device also referred to as calf pumps can facilitate post-operative blood flow when patients are bedbound.
6. Chemical methods. Use either LMWH injections or a NOAC tablet as part of prevention.

Accurate and prompt diagnosis of DVT is necessary because thrombosis left untreated can cause life-threatening complications like PE. Remember, prevention is always better than cure in this instance.

References

1. Al-Hameed F, Al-Dorzi HM et. al. “The Saudi clinical practice guideline for diagnosis of the first DVT of the lower extremity” Ann Thorac Med 2015;10 3-15
2. Whiting PS, White-Dzuro GA et. al. “Risk factors for DVT following orthopedic trauma surgery: an anlysis of 56000 patients.” Arch Trauma Res 2016;5 e32915
3. Adam SS, Key NS et. al.) “D-dimer antigen: current concepts and future prospects.” Blood 2009;113:2878-2887
4. Osman AA, Weina J et. al. “Deep venous thrombosis: a literature review” Int J Clin Med,2018;11(3):1551

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