Last of Three Parts
Diagnosis and Treatment
The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger). In type 1 diabetes, these symptoms develop rapidly, while they develop slowly or subtly in type 2 diabetes Read: EXPLAINER DIABETES part 2 of 3
Several other non-specific signs of diabetes are the following: blurred vision, headache, fatigue, slow healing of wounds, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Long-term vision loss can also be caused by diabetic retinopathy.
DIABETIC EMERGENCIES RECAP
People (usually with type 1 diabetes) may also experience episodes of diabetic ketoacidosis (DKA), a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness. This is caused by heightened levels of ketones from unhealthily excessive fat breakdown and eventual acidification of the blood. A rare but equally severe possibility is hyperosmolar hyperglycemic state (HHS), which is more common in type 2 diabetes and is mainly the result of extreme dehydration.
While the main problem of diabetes is high blood sugar (hyperglycemia) and treatment is essentially aimed to lower it, there is such a thing as treatment-related low blood sugar (hypoglycemia) as a side effect. Treatment options and drugs for diabetes will be discussed in this article.
DIAGNOSIS of DIABETES
According to the American Diabetes Association (ADA) a physician will have the patient take one or more of the following blood tests to confirm the diagnosis:
An HbA1C Test is a test measures the average blood sugar level over the past 2 or 3 months. An HbA1C below 5.7% is normal, between 5.7 and 6.4% indicates prediabetes, and 6.5% or higher indicates diabetes. Sugars like glucose, galactose and fructose spontaneously bond with hemoglobin a blood protein, so high HbA1C indicates the blood has been high of glycated hemoglobin or sugar linked hemoglobin for 2-3 months.
Fasting Blood Sugar Test. This measures the blood sugar after an overnight fast (not eating). A fasting blood sugar level of 99 mg/dL or lower is normal, 100 to 125 mg/dL indicates prediabetes, and 126 mg/dL or higher indicates diabetes.
Glucose Tolerance Test. This measures blood sugar before and after drinking a liquid that contains glucose. Fasting (not eating) overnight is also required before the test and blood is drawn to determine fasting blood sugar level. After drinking, blood sugar is again checked 1 to 3 hours after. a blood sugar level of 140 mg/dL or lower is considered normal, 140 to 199 mg/dL indicates prediabetes, and 200 mg/dL or indicates diabetes.
Random Blood Sugar Test, as the name suggests, is measured at random. A blood sugar level of 200 mg/dL or higher indicates diabetes.
*Results for gestational diabetes can differ.
The physician may further test for autoantibodies and ketones, which may indicate if the diabetes is type 1 or type 2 – auto-antibodies and ketones are more likely seen in type 1 diabetes.
the ADA recommends an active lifestyle and weight loss to most who can tolerate it to prevent the progression of prediabetes to diabetes type 2. A non-sedentary lifestyle, proper diet and exercise also decreases the risk of cardiovascular disease, and may result in a partial or full remission in people with diabetes.
TREATMENT of DIABETES: DRUGS
Insulin is a polypeptide that can get degraded in the gastrointestinal tract that is why it is best administered as a subcutaneous injection instead of a pill.
Insulin Analogs work like normal insulin. Human insulin can be reproduced by recombinant DNA technology using bacteria or yeast. The amino acids of these insulin analogs are altered to produce effects that may be quick or long lasting, thus they are divided between rapid acting (examples are Lispro, Aspart and Glulisine) which works in 30 mins and lasts 5 hours, short acting (regular insulin) which works in 2hrs and lasts for 8 hours. Intermediate acting insulins (NPH Insulin) peak in 8hours and lasts 18hours longer and lastly long acting insulin (Detemir, Glargine and Degludec) lasts between 24 hours or more.
Side effects of insulin injections are hypoglycemia and lipodystrophy – which is an abnormal accumulation or loss of fat in the site of insulin injection. Basically insulin analogs mimic the mechanism of insulin and is usually given to those who have insulin deficiency.
Pramlintide is an amylin mimetic. Amylin is secreted by the beta cells together with insulin. Amylin’s job is to increase insulin’s effectiveness. These drug mimics that effect and as such pramlintide may be used to decrease the dose of insulin injection.
Incretin mimetics are another type of injectable drug. Incretins are hormones released from the Gastrointestinal tract in response to food intake, and they help in signaling the pancreas to release insulin. The two primary incretins are glucagon like peptide 1 (GLP1) and glucose dependent insulinotropic peptide (GIP) – these hormones are inactivated by the enzyme Dipeptidyl peptidase 4 (DPP4) so synthetic GLP1 and GIP are resistant to DPP4. Examples of these drugs are exenitide and liraglutide.
Amylin and incretin mimetics have been said to cause weight loss as well but physicians caution on their use for proposed risks of developing pancreatitis due to their proliferative effect.
The rest of the drugs mentioned are orally taken:
DPP4 Inhibitors – as the name implies, inibit the activity of DPP4, as such enhance the effects of incretins. Drugs belonging to these class usually have gliptin in their names (Linagliptin, Sitagliptin)
Sulfonylureas – to understand this drug, its best to explain how glucose affect the release of insulin from beta cells. Glucose enters beta cells also through GLUT2 transporter and gets converted into pyruvate and goes into the krebs cycle to produce ATP. Inside the B cells are ATP dependent Potassium channels that as the name implies helps potassium get into the beta cells. These channels are blocked by rising levels of ATP thus stopping Potassium from going into the cell creating a depolarization effect that opens Calcium channels. Calcium helps insulin formed from the beta cells out towards the blood stream.
Sulfonylureas act towards these ATP dependent Potassium channels much like ATP thus activating a cascade that releases insulin. Glimepiride, Glipizide are examples of sulfonylurea drugs.
Another group of drugs called Glinides, act on the same ATP dependent potassium channels in beta cells but on a different binding site than sulfonylureas. The difference is that they are more rapid. Drugs belonging to these class have glinides in their names.
Metformin, one of the most common and a first line agent in the treatment of type 2 diabetes is a Biguanide. The mechanism of action of Biguanides are not entirely understood. In diabetes, the body thinks the cells lack glucose even though there is excess glucose in the blood so the liver and other organs try to break down their storages, perhaps of glycogen to form glucose. Metformin’s main action is decreasing the production of glucose from the liver by stopping glycogenolysis and increasing insulin sensitivity in the cells, thus helping glucose trapped in the blood stream to be utilized in the body and saving glycogen stores. Metformin is contraindicated in patients with renal diseases or heart failure because its side effects are decreasing hepatic uptake of lactate which could increase the risk of lactic acidosis
Thiazolidinediones which include the drugs pioglitazone and rosiglitazone, increase glucose and insulin sensitivity by binding to Peroxisome proliferator-activated receptor gamma (PPAR gamma) which codes for proteins responsible for regulating glucose and insulin signaling – the effect is increase in insulin sensitivity.
Sodium glucose co transporters (SGLT) are located in the kidneys and are responsible for glucose reabsorption or excretion in the urine. SGLT inhibitors are drugs that inhibit these transporters and thus inhibiting glucose reabsorption into the bloodstream, making the body increase glucose excretion in the urine. The osmotic diuresis effect of these drugs provide mild decrease in blood pressure, although they may increase symptoms of thirst and urination. Increased incidence of urinary tract infection due to increased glucose in the urine are common side effects.
Alpha glucosidase inhibitors block the enzyme alpha glucosidase located in the intestines that break down carbohydrates into glucose – this delays the increased levels of glucose in the blood. Although the disadvantages are that it creates significant GI side effects due to prolonged accumulation of carbohydrates in the intestines.
Consultation with a physician is a requirement to determine which drug best suits a patient, as one drug or the other may work better than the rest and a similar effect may not be replicated in a different patient. Some of them may cause hypoglycemia and various side effects, some may not be suitable for patients with other types of diseases accompanying diabetes, as such it is imperative to seek consultation before partaking, administering or changing medicines.
Source: Harrison’s Principle’s of Internal Medicine 20th edition
DIABETES in the CONTEXT of COVID-19
According to a study published in the New England Journal of Medicine titled “New-Onset Diabetes in Covid-19”, it stated that there is a bidirectional relationship between Covid-19 and diabetes. On the one hand, diabetes is associated with an increased risk of severe Covid-19. On the other hand, patients with Covid-19 with no prior diagnoses of diabetes have been observed to suddenly acquire new-onset diabetes and severe metabolic complications of preexisting diabetes, including diabetic ketoacidosis and hyperosmolarity for which exceptionally high doses of insulin are warranted. As such, as always, precautions are imperative in these times.