Strategies for Preventing Metabolic Disorders

Metabolic disorders and abnormalities are either primary or genetically inherited disorders that disrupt the body’s normal metabolism. Underlying causes of inherited metabolic disorders are genetic mutations or gene defects responsible for synthesizing various enzymes that regulate metabolism. In primary metabolic disorders, abnormal chemical reactions occur in the body, disrupting metabolism.

More than 600 metabolic disorders have been reported so far. All of them have different systems. Inherited metabolic disorders present shortly after birth or a few months after birth, and primary metabolic disorders may present anytime in life.

What are primary metabolic disorders? 

Metabolism refers to a complex biochemical process that regulates the functioning of the human body. It consists of anabolism or catabolism. In anabolism, your body consumes energy and makes new building blocks, mainly cells and tissues. In catabolism, larger molecules break down into smaller ones, releasing energy. Enzymes balance these two processes. In metabolic disorders, abnormal reactions disrupt this balance. For example, diabetes interferes with the regulation of insulin in the body. 

Metabolic syndrome is a complex of conditions that occur simultaneously and increase the risk of several morbidities like stroke, hypertension, diabetes, and obesity. These conditions include increased blood pressure, high levels of cholesterol and triglycerides, and high blood sugar levels. 

Common Metabolic disorders

The National Center for Advancing Translational Sciences reports more than 500 metabolic disorders. The most common disorders of them are discussed below:

1. Diabetes Mellitus

Diabetes is a condition in which the regulation of blood glucose levels by insulin is disturbed. According to the American diabetic Society, 37.3 million people reported having diabetes in 2019, making up 11% of the population. Most types of diabetes mellitus are:

Type 1 diabetes

An autoimmune disorder occurs when the immune system kills the cells of the pancreas that secrete insulin. Insulin medications are helpful in this condition. 

Type 2 diabetes

In this condition, the body becomes resistant to insulin. The insulin production is normal, but the body cannot use it. It results from a sedentary lifestyle and a poor diet. 

2. Gaucher’s Disease

This is a genetic disorder that results from mutations in genes that are responsible for the production of glucocerebrosidase. Decreased levels of glucocerebrosidase lead to the accumulation of fats in the body. Accumulation of fats in the spleen and liver results in hepatomegaly and splenomegaly. Most people with Type 1 Gaucher’s disease present with tiredness and easy bruising. 

3. Hemochromatosis

It results from the accumulation of excessive iron in the body due to HFE gene mutation. Iron buildup in the body leads to fatigue, weakness, pigmentation of the body, gastric pain, joint pain, and sexual difficulties. 

4. Mitochondrial disorders

These are complex conditions that affect the production of energy in mitochondria. Energy production is necessary for the proper functioning of cells. Genetic mutations, which run in families, are responsible for this disorder. 

These disorders can target any part of your body. For example, these genetic mutations in pancreatic cells can cause diabetes, and some cells may lead to decreased muscle growth.  

5. Phenylketonuria (PKU)

Phenylketonuria (PKU) occurs due to decreased levels or deficiency of phenylalanine hydroxylase. This enzyme regulates amino acid metabolism to build proteins necessary for growth and development. 

Due to deficiency of phenylalanine hydroxylase, an excessive number of amino acids accumulate in the brain leading to brain damage. 

A musty odor in the breath, sweat, skin, and urine, seizures, skin rashes, microcephaly, intellectual disability, and psychological problems are the most common symptoms of PKU. 

Causes of Metabolic disorders:

Metabolic syndromes are closely linked with inheritance (genetically inherited disorders), obesity, and a sedentary lifestyle. It may be linked with insulin resistance, dietary habits, and high triglycerides levels. 

Genetically inherited disorders are due to genetic mutations (for example, Gaucher’s disease). Mitochondrial dysfunction also predisposes to metabolic disorders. Organ dysfunction (i.e., pancreas in diabetes) may also lead to these disorders. 

What are the risk factors for metabolic disorders?

The following factors increase the risk of metabolic disorders in your body. 

Age: The risk of metabolic disorders increases with age. Older people are prone to developing many disorders like hypertension, diabetes, and high triglycerides levels. 

Obesity: Having too much weight around your belly and waist is dangerous. It increases the risk of metabolic disorders. Cholesterol and triglycerides levels increase with obesity, which may lead to atherosclerosis resulting in heart diseases. 

Ethnicity:In the United States, Hispanics — especially Hispanic women — appear to be at the greatest risk of developing metabolic syndrome. The reasons for this are not entirely clear.

Diabetes: Family history of diabetes mellitus and gestational diabetes are two major risk factors for diabetes. It occurs when the regulation of insulin hormone is disrupted in the body, leading to high blood sugar levels. 

Sedentary lifestyle: Sedentary lifestyle, smoking, and alcohol intake are risk factors for various conditions. It leads to obesity, which is the root of all disorders.

Comorbidities: Other conditions like NAFLD (Non-alcoholic fatty liver disease), PCOS (polycystic ovarian syndrome), and sleep apneas increase the risk of metabolic disorders. 

What is the common age of onset?  

The prevalence of metabolic disorders in people aged 20-29 years is 6.7% and 40%  in people aged more than 60  years or more. 

According to research statics on metabolic syndrome in the US population, about 44% of people aged 50 years or more had metabolic syndrome. 

What are early warning signs of metabolic disorders? 

Signs and symptoms of metabolic disorders vary with the underlying cause. Most of them are asymptomatic in the early stages. Signs of insulin hormone dysfunction or resistance leading to diabetes are high blood sugar, neuropathy, nephropathy, retinopathy, increased thirst, and urination. 

Most disorders present with increased BMI and fats around the waist and abdomen. Fatigue, increased thirst, lethargy, abdominal pain. 

Metabolic syndrome is associated with other medical conditions due to high blood pressure, increased cholesterol levels, triglycerides, and blood glucose. 

How are metabolic disorders diagnosed? 

The following methods diagnose metabolic disorders: 

• Basic laboratory tests 
• Acid-base status 
• Anion gap 
• Blood glucose levels 
• Ammonia levels
• Lactic acid levels 
• Urinary Ketones levels 

Additional considerations include the following tests: 

• CBC
• LFTs
• Coagulation studies 
• BUN 
• Uric acid 
• Lipid levels 
• CSF cell study
• CSF glucose levels 
• Non-laboratory tests include X-ray, CT scan, MRI, MR, and spectroscopy. 
• Biomarkers are indicators of certain diseases. For example, creatine kinase indicates certain diseases like glycogen storage diseases and Pompe disease.

According to revised guidelines of the National Heart, Lung, and Blood Institute (NHLBI) and the American Heart Association (AHA) in 2005, if a person fulfills 3 out of these 5 criteria, he has metabolic syndrome.

1. Fasting glucose levels ≥100 mg/dL (or on drug therapy for diabetes)
2. Blood pressure ≥130/85 mm Hg (or on drug therapy for high blood pressure)
3. Triglycerides levels in blood ≥150 mg/dL (or receiving statins)
4. HDL-C < 40 mg/dL in male patients or < 50 mg/dL in female patients (or getting drug therapy for reduced HDL-C)
5. Waist circumference ≥102 cm in males or ≥88 cm in females.

How to prevent and treat metabolic disorders? 

Metabolic disorders can be prevented and treated by lifestyle changes and medical interventions.

Lifestyle changes:

Lifestyle changes are the first and foremost therapeutic interventions to prevent metabolic disorders. Diet and weight loss have ascertained a role in managing metabolic disorders, but patients and doctors usually overlook lifestyle changes. Cardiovascular risk is the cornerstone of metabolic disorders; lifestyle changes have shown many favorable effects in preventing cardiovascular disorders. 

The following interventions are helpful in the prevention and treatment of metabolic disorders: 

1-Manage your weight. Weight loss and healthier lifestyle interventions keep your BMI within normal limits. 

2-Exercise and physical activity burns extra calories, reduce fats, and keeps you healthy. 

3-Eat healthy. Maintain your BMI below 25. Choose meals with high dietary fibers and have Mediterranean meals. Vegetables, fruits, nuts, roots, whole grains, and olive oils are helpful. 

4- Quit smoking.

5- Limit alcohol intake. 

6-Focus on lifestyle. 

Medical Interventions: 

Medical interventions depend on the underlying cause. These include maintaining blood pressure, lipid profile (triglycerides, LDL, and HDL), and blood sugar levels. Adhere to medical advice from your physician. 

A research study indicates probiotics that affect the gut flora are used as a complementary treatment. Probiotics stimulate your immune system, improve lactose tolerance, and help relieve diarrhea and inflammation. They often improve gut dysbiosis linked with obesity. They have proven effects in the restoration of mucosal barrier integrity and immunomodulation. 

Research studies have also demonstrated that the Inhibition of Nicotinamide N-methyltransferase helps relieve metabolic disorders. 

What are the complications of metabolic disorders?  

Metabolic disorders are associated with several complications. These include coronary artery disease, heart failure, venous thromboembolic disease, ischemic heart diseases, aortic stenosis, diabetes mellitus, pulmonary vascular disease, and right heart failure. 

Research studies and clinical data have demonstrated an increased risk of ischemic stroke in people with metabolic disorders. These disorders are also linked with breast cancer, carcinoma of kidneys, lungs, prostate, and gallbladder. In pregnant females, metabolic disorders increase the risk of pre-eclampsia. 

Additional research studies indicate the effects of these disorders on neurocognitive performance. They accelerate the process of cognitive impairment and aging.

Paradoxically, metabolic disorders lessen the risk of bone fracture and decreased bone mineral density.