By: Archana Murugan, PharmD Candidate c/o 2029
Overview
Diabetes is a chronic disease caused by insufficient or absent insulin secretion leading to high blood sugar levels in the body. Diabetes is mainly characterized by two types: type 1 and type 2.
In type 1, the body makes insufficient or no insulin and the immune system destroys cells in the pancreas that make insulin. This type is usually diagnosed earlier in childhood and young adulthood. In type 2 diabetes, cells do not use insulin properly to maintain the normal glucose range. This type is the most common and risk factors include obesity or family history. Gestational diabetes is a type of diabetes that develops in pregnancy and usually “goes away after the baby is born” but the mother is at higher risk of developing type 2 diabetes.Less commonly, diabetes is caused by a single-gene mutation (monogenic diabetes) or from removal/damage of the pancreas due to inflammation or other causes.1
Uncontrolled diabetes Complications
Consistent elevation in blood glucose levels poses several chronic and acute risks to every major organ in the body. Acute complications occur rapidly and are medical emergencies. Chronic complications are characterized by long-term damage to the body from persistent hyperglycemia.
Acute complications include diabetic ketoacidosis (DKA), hypoglycemia, and hyperglycemic states. DKA is caused by severe insulin deficiency that leads to ketone production and eventually metabolic acidosis. Characterized by dehydration, abdominal pain, and Kussmaul respiration, DKA can progress to shock or coma if untreated. Hypoglycemia, often due to missing medications or meals, can cause sweating, loss of consciousness, seizures, etc. Hyperglycemia due to inadequate insulin can lead to dehydration, electrolyte imbalance, and can be life-threatening.2
Chronic complications include macrovascular disease, microvascular disease, diabetic foot, and increased infection risks. Macrovascular diseases refer to atherosclerotic damage to large vessels such as coronary artery disease, stroke, etc. Microvascular disease includes diabetic retinopathy which is the leading cause of blindness in the Western world, diabetic nephropathy which is progressive damage and possible renal failure, and diabetic neuropathy. Diabetic neuropathy is characterized by sensory loss, pain, and muscle atrophy. Additionally, patients have tachycardia, orthostatic hypotension, GI dysmotility, and urinary issues. Patients have diabetic foot which Is a combination of neuropathy and poor circulation leading to ulcer, infection, and gangrene. These conditions may or may not require amputations.2
Most deaths (~75%) in type 2 diabetes are due to cardiovascular disease. 2 Cardiovascular disease is subdivided into coronary artery disease, heart failure, arrhythmias, and autonomic neuropathy.
Statistics
The National Diabetes Statistics Report from the CDC offers the most current data on how common diabetes and prediabetes are, how many new cases occur each year, factors that increase complications, and impact. According to the report, “the percentage of adults with diabetes increased with age, reaching 28.8% among those aged 65 years or older.”3
- 40.1 million people of all ages in the United States had diagnosed or undiagnosed diabetes in 2023.
- Adults aged 18 years or older with diabetes: 39.8 million. This is 14.9% of U.S. adults.
- Adults 18 years or older with undiagnosed diabetes (unaware they have it): 11.0 million. This is 4% of all U.S. adults or 27.6% of all U.S. adults with diabetes.
According to the report, 4.8% of adults with diabetes do not have usual place of care which limits consistent monitoring and early intervention. Lifestyle risks remained common with many adults reporting smoking, high rates of obesity, lack of exercise, leisure, and transportation issues.3 Clinically, a substantial proportion have elevated A1C, high blood pressure, or high non‑HDL cholesterol, all of which accelerate vascular and organ damage. These conditions or risk factors emphasize the ongoing challenges of achieving optimal diabetes control and preventing long-term complications such as cardiovascular disease, CKD, neuropathy, and vision loss.
In preventing and reducing complication risks, many adults engage in protective health behaviors.
- 36.4% meet recommended physical activity goals
- 56.6% report actively managing or losing weight to reduce disease risk
- Medications: 66.1% of adults aged 40-75 take statins/cholesterol-reducing therapies to prevent cardiovascular diseases
However, only 14.9% meet all four ABC targets relating to A1C level of <7%, blood pressure of <130/80 mmHg, non-HDL cholesterol <130 mg/dL, and nonsmoking status. Strong adherence to routine monitoring was demonstrated with 92.6% of the necessary yearly tests for blood pressure, cholesterol, and A1C being obtained. Additionally, 65.8% of people have had an influenza vaccination, indicating a high vaccination uptake.3 Overall, these findings demonstrate that even though diabetic patients engage in preventive care, there is still significant room for improvement in terms of attaining thorough risk-factor control.
Case Reports
A systematic search from PubMed, ScienceDirect, and other scholarly databases was performed, and a series of case reports on metformin toxicity were analyzed and condensed.
A total of 242 individual cases were reviewed, drawn from 158 case reports and 26 case series, with an overall mortality rate of 19.8%. Among these patients, 88.4% had diabetes and were taking metformin. While 57 patients (23.6%) had an acute overdose, the majority (76.4%) developed toxicity while on standard therapeutic doses. Metformin‑associated lactic acidosis (MALA) was the predominant adverse effect, reported in 224 cases (92.6%). The majority of patients had neurological and GI symptoms when they first arrived, and many had severe metabolic acidosis with high lactate levels. Vasopressors (58.7%), invasive mechanical ventilation (52.9%), and renal replacement therapy (68.6%) were frequently needed.4 Toxin removal, renal dysfunction management, and MALA correction were main uses of RRT. Prompt therapy improved outcomes in patients with severe acidosis conditions and elevated lactate/metformin levels.
Conclusion
Diabetes remains a major public health challenge, not only because of its growing prevalence but also due to the significant complications seen when poorly controlled. The data presented here emphasizes the importance of age, lifestyle factors, and access to care in the management of the disease, as well as the outcomes of the disease process. It is pertinent to closely monitor disease progression, as even small changes can result in either short or long-term effects. Consistent monitoring, patient education, and management are all key steps to take in improving the overall trajectory of diabetes care.
REFERENCES:
- Bessesen D. What is diabetes? National Institute of Diabetes and Digestive and Kidney Diseases. Published 2023. https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes.
- Farmaki P, Damaskos C, Garmpis N, Garmpi A, Savvanis S, Diamantis E. Complications of the Type 2 Diabetes Mellitus. Curr Cardiol Rev. 2020;16(4):249-251. doi:10.2174/1573403X1604201229115531.
- Centers for Disease Control and Prevention. (2026) National Diabetes Statistics Report, 11 Mar 2026. Available at https://gis.cdc.gov/grasp/diabetes/diabetesatlas-statsreport.html. (Accessed: 03/17/2026).
- Juneja D, Nasa P, Jain R. Metformin toxicity: A meta-summary of case reports. World J Diabetes. 2022;13(8):654-664. doi:10.4239/wjd.v13.i8.654.
