Diabetes Management Updates

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Introduction   

Diabetes Mellitus (DM), also known as diabetes, is a condition in which the body develops high levels of blood glucose due to the inability to produce insulin or for the cells to use insulin (1) effectively. If left untreated or mismanaged, it can lead to health complications such as heart disease, chronic kidney disease, blindness, nerve damage, oral and mental health problems (1)(15).  

There are several classifications of DM, and the following will be discussed: T1DM, T2DM, gestational diabetes, and idiopathic diabetes. 

Classifications of Diabetes

Type 1 Diabetes Mellitus (T1DM)  

T1DM is formerly known as juvenile diabetes or insulin-dependent diabetes and usually occurs in children and young adults (1). Although, it can also occur at any age and accounts for 5 – 10% of cases. T1DM develops when one’s own immune system attacks and destroys the beta cells that produce insulin in the pancreas (6).     

Type 2 Diabetes Mellitus (T2DM)  

T2DM, formerly known as adult-onset diabetes or non-insulin-dependent diabetes, develops because of the body's inability to use insulin effectively. It is the most common type of diabetes and mainly occurs in adults aged 30 years and older (1). However, it is also becoming common in children and young adults due to obesity. It accounts for 90% of the population diagnosed with diabetes (6).   

Gestational Diabetes 

Gestational Diabetes occurs during pregnancy and in women who have never had a previous diagnosis of diabetes. It is a result of pregnancy hormones that are produced by the placenta or because of the insufficient use of insulin by the cells (1). Gestational diabetes can be temporary or in some cases can become chronic. It is also likely that children whose mothers have gestational diabetes can develop diabetes later in life (6).  

Prediabetes 

Prediabetes, also referred to as impaired glucose tolerance, is a stage when a person is at risk of developing diabetes. If well managed through proper diet management and exercise, this can help with the prevention or delay of type 2 diabetes (1).  

Other Forms of Diabetes 

Other forms of diabetes include monogenic diabetes syndrome, diabetes from the removal of the pancreas or damage to the pancreas from disease processes such as pancreatitis or cystic fibrosis, and drugs or chemical-induced diabetes from glucocorticoids used to treat HIV/Aids or organ transplant (1) (6).  

Statistical Evidence/Epidemiology 

Diabetes is now ranked as the 8th leading cause of death in the United States (6). There is no known cure for diabetes. It is one of the fastest-growing chronic diseases and the most diagnosed noncommunicable disease. It is also one of the leading causes of chronic kidney disease, adult blindness, and lower limb amputations (6).   

In 2019, it was estimated that 37.3 million American adults have diabetes, which equals 11.3% of the population (4). Of those, 41% were men and 32% were women. 28.7 million were diagnosed with diabetes, and 8.5 million were undiagnosed.  

There are 96 million American adults who are prediabetic, which means they are at risk of developing diabetes, but their blood glucose levels are not high enough to be diagnosed with diabetes (5).  

Most of the population that is pre-diabetic is 65 years old or older. Type 2 diabetes accounts for 90% to 95% of cases (5). The risk of developing diabetes increases with age.  

The prevalence of diabetes is much higher in both black and Hispanic/Latino adult men and women. Men are more likely to develop diabetes compared to women. Due to the rise in obesity in younger adults, there has been an increase in the number of new cases of diabetes in black teens (4).  

The figure below represents trends in incidence of type 1 and type 2 diabetes in children and adolescents 2002–2018; results show the incidence of type 2 diabetes has significantly increased (4)

Etiology and Pathophysiology 

In normal glucose metabolism, blood glucose is regulated by the two hormones insulin and glucagon (11). Insulin is secreted by the beta cells in the Islet of Langerhans in the pancreas and glucagon is secreted by the alpha cells in the pancreas.  

When there is an increase in blood glucose, the function of insulin is to reduce blood glucose by stimulating its uptake in the cells. Glucose is stored as glycogen in the liver and muscles or as fat in the adipose tissues. When blood glucose levels start to fall, glucagon promotes the release of glycogen from the liver, which is used as a source of energy in the body (8) (13).   

When there is a deficiency of insulin or a decreased response of insulin on the targeted cells in the body, it leads to hyperglycemia (high blood glucose). Meaning that the glucose that remains in the blood is not able to get to the cells. Diabetes develops mainly because of lifestyle and genetic factors (13).

T1DM 

The etiology is not well understood, though it is thought to be influenced by both environmental and genetic predispositions that are linked to specific HLA alleles. T1DM is considered an autoimmune disorder that is characterized by T-cell-mediated destruction of the pancreatic B-cells (13).  

As a result, this leads to complete insulin deficiency and ultimately hyperglycemia, which requires exogenous insulin. The rate of destruction of the pancreatic B-cell-specific disorder is known to develop rapidly in infants and children or gradually in adults (8)(13). 

T2DM 

The etiology of T2DM is characterized by decreased sensitivity to insulin and decreased secretion of insulin. Insulin resistance occurs due to the disruption in the cellular pathways that result in a decreased response in the peripheral tissues, particularly the muscle, liver, and adipose tissue.  

T2DM diabetes can progress slowly and asymptomatically over a period. Obesity and age can play a key role in the homeostatic regulation of systemic glucose because they influence the development of insulin resistance, which affects the sensitivity of tissues to insulin. Therefore, most patients with type 2 diabetes are overweight or obese 7) (8).

Diagnostic and Screening tools 

There are a variety of tests that are used to diagnose and monitor diabetes. These vary based on the type of symptoms that a patient may have. Diagnosis of DM requires at least two abnormal test results, which should include fasting glucose and A1C. The tests should be one of two from the same sample or two abnormal test results drawn on different days (3). 

The recommended diagnosis guidelines for diabetes must be based on the following criteria: 

• Fasting Plasma Glucose (FPG) concentration with results greater than 126 mg/dL. This test involves measuring blood glucose at a single point. To have accurate results, the test should be conducted after one has had nothing to eat or drink for at least 8 hours (3). 
• Glycated hemoglobin (Hb A1C) is indicative of the average levels of blood glucose in a period of two to three months. Results greater than 6.5% mean diagnosis of diabetes. This blood test does not require fasting. The A1C test is not suitable for pregnant women or those who have certain blood conditions (anemia) - NIDDK. This test should only be used for prediabetes screening (3). 
• Oral Glucose Tolerance Test (OGTT): prior to conducting this test, an FPG level needs to be measured. One must ingest 75 grams of glucose liquid. Thereafter, their glucose level is measured 2 hours after they have taken the liquid. Test results greater than 200 mg/dL are indicative of diabetes. This test is commonly used in pregnant women (3). 
• Random plasma glucose of 200 mg/dL. This test is suitable when one has symptoms of hyperglycemia, which are polydipsia, polyuria, and polyphagia (3).  

Screening 

Screening is generally recommended for adults aged 45 or older regardless of present risk factors. The updated recommendation guidelines for prediabetes screening include adults 35 years and older who are overweight or obese (3).  

Screening for Prediabetes 

Prediabetes is associated with the impairment of blood glucose levels between 100 – 125 mg/dL. The diagnosis of prediabetes should be confirmed with glucose testing when there is impaired glucose tolerance with plasma levels between 140 – 199 mg/dL 2 hours after one has ingested 75g of oral glucose. A1C levels of prediabetes are between 5.7% to 6.4% (3). 

Screening for Pregnant women 

It is recommended that all pregnant women between 24 – 28 weeks be screened for gestational diabetes to avoid missing those that are at risk. A positive 3-hour OGTT test of greater than 140 mg/dL meets the criteria for diagnosis (3).  

Medication Management 

Monitoring of blood glucose levels in patients is useful in determining the effectiveness of antidiabetic medication. To achieve better patient outcomes, it is important to recognize individual needs (11).  

It is recommended that the approach to medication management should be based on each patient's hyperglycemic index and should include the following: the presence of comorbidities, risk of hypoglycemia, vascular disease, life expectancy, and disease duration (3).   

When the management of diabetes cannot be achieved through diet and exercise alone, oral antidiabetic agents are the preferred treatment (14). Oral antidiabetics can help maintain and achieve glycemic goals for patients who are diagnosed with T2DM) (10)(14).  

Diabetes Education and patient engagement is essential to managing diabetes (11). There are several classes of anti-diabetic medication. Below are some of the most utilized antidiabetic medications (9)(14).  

Biguanides 

Metformin is the only medication in this category. 

• It is considered the 1st line of treatment in patients with T2DM unless contraindicated. 
• Metformin helps to decrease hepatic glucose production.  

• Decreases intestinal absorption of glucose by improving insulin sensitivity. Must be titrated initially to minimize adverse effects. 
• Avoided in clients with chronic kidney disease.  
• Side effects: Lactic acidosis, hypoglycemia. 

GLP 1- Receptor Agonists (RAs) 

Mimics glucagon-like peptide 1 (GLP -) hormone. Binds to GLP-1 receptors stimulate glucose-dependent insulin release and delay gastric emptying, which increases satiation.  

• Known to have cardiovascular benefits. 
• Can be taken orally or subcutaneously.  
• Special considerations: Can cause weight loss, GI side effects such as nausea, vomiting and diarrhea, dehydration, increased satiation (fullness), acute pancreatitis, and reactions at the injection sites.  
• Some labels may require renal dose adjustment.  
• GLP - 1 RAs should be considered before starting clients on insulin to help reduce A1C then oral antihyperglycemic medications are not effective in treating diabetes.  

Sulfonylureas 2nd generation 

Stimulates insulin release in pancreatic beta cells.  

• Risk for prolonged hypoglycemia. Therefore, it should be avoided with the concurrent use of insulin.  
• Can cause weight gain.  
• Can cause photosensitivity.  
• Avoid use in clients with sulfa allergies and photosensitivity.  
• Avoid use in clients with chronic kidney disease and liver disease.   

Dipeptidyl Peptidase (DPP) - 4 inhibitors 

Prevents DPP-4 enzymes from breaking down to GLP-1 hormone.   

• Neutral weight.  
• Monitor for acute pancreatitis, which can cause joint pain.  
• May require renal dose adjustment with these brands: Saxagliptin (Onglyza), Sitagliptin (Januvia), and Alogliptin. Linagliptin does not require dose adjustment.  

Sodium-Glucose transporter - 2 (SGLT-2) inhibitors 

Reduce the reabsorption of glucose by up to 90%, therefore promoting the exclusion of glucose from the body.  

• Known to have cardiovascular benefits for clients with cardiovascular disease.  
• Use with caution in clients with increased risk of fractures.  
• Avoided in clients with diabetic ketoacidosis and those prone to have frequent urinary tract infections.  
• This medication should be avoided in clients with pure poor kidney function due to volume depletion and hypotension.  
• There’s also a risk for Fournier gangrene.  

Thiazolidinediones 

Pioglitazone and rosiglitazone can help reduce insulin resistance which promotes improved sensitivity to insulin. As a result, it can help reduce the A1C levels.  

• Can cause weight gain.  
• Potential risk for heart failure when taking thiazolidines (brands: pioglitazone, rosiglitazone). 
• Generally, it is not recommended for clients with renal impairment as medication has the potential to cause fluid retention.  
• Risk for bone fractures, bladder cancer, and increased LDL cholesterol (rosiglitazone).  

• Thiazolidines do not cause hypoglycemia and can be used in combination with other antidiabetic medications including insulin. 

Insulin therapy 

Insulin therapy is commonly recommended for patients with T1DM. It can be used to help prevent the development and progression of diabetes (2). The ideal insulin regimen should be tailored based on individual needs and glycemic targets to better contend with physiological insulin replacement to maintain normoglycemia. Insulin therapy is also recommended for patients with hemoglobin A1c of greater than 9% - 10% and when symptoms of hyperglycemia are present (3).  

Other Diabetes Interventions 

The automation of glucose monitoring devices and insulin delivery systems is revolutionizing glucose management mainly because it promotes lifestyle flexibility and improved glucose management (2). 

• Glucose Monitoring Devices- these devices are ideal for clients who are on insulin regimens and may become the standard for assessing glycemic controls in clients with DM (7). 
• Continuous Glucose Monitoring (CGM)- devices that are inserted subcutaneously and measure interstitial blood glucose levels. CGMs are devices that are used to provide glucose readings, trends, and alerts to the user in real-time to inform diabetes treatment decisions. (2)(3) 

• Importance- CGM is recommended for all patients with diabetes who receive treatment with intensive insulin therapy, defined as three or more insulin injections per day for all individuals with hypoglycemia (frequent, several, nocturnal) (3).  
• Known to reduce hyperglycemia and A1C levels. 

• Insulin Pump Therapy- also known as Continuous Subcutaneous Insulin Infusion (CSII) has had notable advances over the years. CSII is recommended for those with type 1 diabetes, although in recent studies, conventional CSII is also recommended for use in T2DM patients (2)(3). CSII is a small computer that is programmed to deliver fast-acting insulin continuously to the body using mechanical force via a cannula that is inserted under the skin (2).  

• It is more precise and flexible in insulin dosing. 
• Known to improve glycemic control.  
• Cheaper than using Multi-Dose Insulin. 

• Automated Insulin Delivery Systems (AIDS) - This is a diabetes management system that utilizes an insulin pump in conjunction with an integrated CGM and computer software algorithm (3).  

• Advantages: precision and flexibility with insulin dosing. 
• Recommended for T1DM: Achieve glycemic targets with less burden. 

Upcoming Research  

Islet cell transplant has been a biological solution to help treat patients with T1DM due to poor graft survival rates. Future research will focus on manipulating the beta cells in the pancreas to make them more viable. Other treatments that have been recently made available include incretins and Amylin which improve the absorption of insulin in the body (1).  

• The development of other types of insulin that can be administered by inhalation.  
• The development of immunosuppressant drugs that will help treat T1DM. 

Conclusion

Diabetes is a complex disease that requires a multi-disciplinary and patient-centered approach to help with effective management. Regular and early screening are necessary for those at risk for developing diabetes. Most importantly, ease and access to choices of managing diabetes are necessary.

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