Differences between the Types of Diabetes
Type 1 diabetes, also called juvenile diabetes is the most common type of diabetes seen in children and it is characterized by low or absence of insulin production and the patient is dependent on insulin injections for glucose metabolism and prevention of complications like diabetic ketoacidosis. The etiology has been reported to be immune-mediated or idiopathic. Human leukocyte antigen (HLA) class II is linked most with the susceptibility to develop the disease, however, most children with type I DM have no positive history in their families and the occurrence of the disease has been linked to other factors such as viral infections, mumps, enteroviruses that cause beta cell immunity leading to the destruction of the pancreas (Pasi and Ravi, 2022). In contrast, type II DM previously known as adult onset diabetes, and now seen in children as well, is associated with obesity and family history and is characterized by both impaired insulin secretion and insulin resistance. It is a progressive disease that begins with insulin resistance but as long as the pancreatic beta cells are able to secrete sufficient insulin to compensate for insulin resistance, glucose levels are maintained at relatively normal levels. Diabetes becomes evident when beta cells no longer secrete sufficient insulin to maintain normoglycemia. The severity of the disease increases over time due to increase in the impairment in insulin secretion (Taylor, Yazdi and Beitelshees, 2021).
Gestational diabetes (GDM) is another type of diabetes and the American Diabetes Association describes GDM as any degree of glucose sensitivity with onset or first detection during pregnancy while pre-gestational diabetes includes Type I and type II DM that occurs before pregnancy. GDM presents during the second or third trimester of pregnancy and is precipitated by changes in the body’s metabolic state during pregnancy that significantly affects insulin action and sensitivity. This leads to insulin resistance and consequent hyperglycemia. Contributory factors include obesity, family history, prediabetes state, increased maternal age and ethnicity (Choudhury and Rajeswari, 2021). Blood sugar levels return to normal soon after delivery. However, if hyperglycemia persists after delivery, it should be appropriately diagnosed and treated as type II diabetes.
Metformin and Type II DM
For this discussion, I have selected type II DM and metformin as a pharmacological treatment for type II DM. There are twelve classes of drugs approved to treat type II DM: biguanides (for example metformin), sulfonylureas, thiazolidinediones, DPP4is, SGLT2is, GLP1RAs, insulins, alpha-glucosidase inhibitors, dopaminergic antagonists, bile acid sequestrants, meglitinides, and amylinomimetics. Metformin is a biguanide and a first-line drug of choice for the initial treatment of newly diagnosed type II diabetes. Metformin has also been reported to reduce the risk of developing diabetes and is associated with moderate weight loss (Flory and Lipska, 2019). Metformin lowers blood glucose through different pathways: activation of AMP-activated protein kinase, inhibition of hepatic adenylyl cyclase, inhibition of mitochondrial glycerol-3-phosphate dehydrogenase, increasing levels of growth differentiation factor 15 (GDF15), and alteration of intracellular protein-bound iron levels (Taylor, Yazdi and Beitelshees, 2021).
Metformin decreases hepatic glucose production. Its action occurs mostly in the gut independent of absorption into the circulation, thereby reducing glucose absorption in the gut. This drug does not stimulate insulin release from the pancreas therefore when used alone, it does not cause hypoglycemia. To support the effectiveness of Metformin in the regulation of blood sugar, the patient should be educated to consume good quality carbohydrates such as diet with low glycemic index or high complex carbohydrates, high fiber, low-calorie, low-fat and minimal processed foods (Flory and Lipska, 2019).
Metformin is an oral medication that is absorbed from the small intestine. It should be swallowed whole with water and is best taken with food in order to minimize the gastrointestinal (GI) side effects. It is not metabolized but is excreted unchanged by the kidneys. This is important to note because if used by people with renal impairment, it can accumulate to toxic levels. Metformin is available in immediate release form in 500, 850 and 1000mg tablets and in extended release form in 500, 750, and 1000mg tablet strength (Rosenthal and Burchum, 2021). Treatment with metformin is to begin with 500mg daily and consider using the ER form to minimize risk of GI adverse effects. Adjust dose gradually to 2000 mg daily if tolerated and as required based on glycemic goal, duration of diabetes, age/life expectancy, comorbid conditions and micro/macrovascular complications. These factors help the practitioner to determine how aggressive they need to be with treatment and to determine when to add another class of drugs. Safety issues and barriers to use of metformin include GI intolerance (nausea and diarrhea), lactic acidosis in patients with impaired kidney function (contraindicated in patients with estimated GFR <30 mL/min), contraindicated in patients with acute heart failure and evidence of end-organ hypoperfusion, and should not be used in the presence of functional hepatic failure or cute liver injury (Flory and Lipska, 2019). Metformin is a drug of choice for patients that skip meals because metformin does not actively lower blood glucose. Metformin can be used alone as the first oral medication at the initial diagnosis of diabetes and it is recommended to initiate treatment early without delay or further attempt to control blood sugar with diet. In younger patients who are overweight, metformin has been reported to reduce the risk of developing diabetes by 31%, however, Metformin is not a substitute for diet and exercise. Diet and exercise for a weight loss of 5 to 7% reduces the average risk for type II diabetes by 58% and for persons older than 60, it reduces the risk by up to 70% (Flory and Lipska, 2019).
Short Term and Long Term Impact of Type II DM
In the short term, type II DM is associated with hypertension, dyslipidemia, microalbuminuria, hyperglycemia, polydipsia, and polyuria, blurred vision, fatigue and headache. Long term, type II diabetes leads to diabetic kidney disease (diabetic nephropathy) which accounts for 30-47% of the end stage renal disease cases and one of the major causes of diabetes-related deaths. In addition, dysfunctions of the cardiovascular system including atherosclerosis, myocardial infarction, heart failure, and cardiomyopathy are the most prevalent causes of morbidity and mortality in patients with diabetes. Other long term effects of diabetes include diabetic retinopathy which occurs in about 40-45% of patients, diabetic neuropathy, non-alcoholic steatohepatitis and liver fibrosis, and most recently, restrictive lung diseases such as lung fibrosis (Demir, Nawroth, Herzig and Ustunel, 2021).
Conclusion
Metformin has been shown to be an effective first-line pharmacologic treatment for type II DM in most patients, however, based on the treatment goal and specific patient factors, an additional pharmacologic intervention may be required to reach glycemic goal. Adverse effects of Metformin may be mitigated by use of the ER form and careful dose titration.
References
Choudhury, A., A., & Rajeswari, V. D. (2021). Gestational diabetes: A metabolic and reproductive disorder. Biomedicine and Pharmacotherapy, 143. https://doi.org/10.1016/j.biopha.2021.112183.
Demir, S., Nawroth, P. P., Herzig, S., & Ustunel, B. E., (2021). Emerging targets in type 2 diabetes and diabetic complications. Advanced Science, 8. https://doi.org/10.1002/advs.202100275Links to an external site.
Flory, J., & Lipska, K. (2019). Metformin 2019. Journal of American Medical Association, 321 (19), 1926-1927.
Pasi, R., & Ravi, K. S. (2022). Type 1 diabetes mellitus in pediatric age group: A rising endemic. Journal of Family Medicine and Primary Care, 11(1), 27-31.
Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.
Taylor, S. I., Yazdi, Z. S., & Beitelshees, A. L. (2021). Pharmacological treatment of hyperglycemia in type 2 diabetes. The Journal of Clinical Investigation, 131(2), doi.org/10.1172/JCI142243.
