A number of risk factors may increase an individual’s risk for developing diabetes, and these risk factors can be classified as nonmodifiable or modifiable. Examples of nonmodifiable risk factors include genetics, gender, ethnicity and age. Examples of modifiable risk factors include obesity, sedentary lifestyle, and diet.

With regard to type 1 diabetes mellitus (T1DM), risk factors can be classified as genetic or environmental. Literature indicates that the lifetime risk of developing T1DM is significantly increased in close relatives of a person with T1DM. Additionally, among genetically susceptible individuals, exposure to one or more environmental agents (e.g., viruses or foods) appears to activate an immune response that eventually causes destruction of the insulin-producing pancreatic beta cells.

According to the American Diabetes Association, risk factors for type 2 diabetes mellitus (T2DM) include one or more of the following:

• Age ≥35 years
• Overweight or obesity
• Sedentary lifestyle
• Family history of T2DM
• History of impaired glucose regulation (prediabetes)
• Gestational diabetes mellitus or delivery of a baby >4.1 kg
• Metabolic syndrome
• Uncontrolled hypertension
• Dyslipidemia (high-density lipoprotein [HDL] cholesterol <35 mg/dL [0.9 mmol/L] or triglyceride level >250 mg/dL [2.8 mmol/L])
• History of cardiovascular disease
• Polycystic ovary syndrome
• African, Hispanic, Asian American, or American Indian ethnicity
• Fatty liver disease
• HIV infection
• History of untreated sleep apnea.

Clinical data reveal that an estimated 80% of all T2DM cases are linked to obesity, and as the obesity epidemic continues to increase, so do cases of T2DM.  

Undiagnosed and/or poorly controlled diabetes is associated with a plethora of complications that can be further classified as microvascular or macrovascular. Diabetes-related morbidity and mortality are a consequence of both macrovascular disease and microvascular disease. Microvascular complications include nephropathy, neuropathy, and retinopathy. Findings from the United Kingdom Prospective Diabetes Study and the Kumamoto; Action in Diabetes and Vascular Disease; and Action to Control Cardiovascular Risk in Diabetes trials showed that improved glycemic control lowers the risk of microvascular complications (principally retinopathy and nephropathy) in patients with T2DM. Retinopathy can be divided into two general classes: nonproliferative (development of microaneurysms, venous loops, retinal hemorrhages, hard exudates, and soft exudates) and proliferative (presence of new blood vessels, with or without vitreous hemorrhage, and a progression of nonproliferative retinopathy). Some studies show that at the time of diagnosis, some patients exhibit signs of chronic kidney disease, peripheral arterial disease, heart failure, and cardiovascular disease.

Macrovascular complications associated with diabetes include coronary artery disease, cardiomyopathy, arrhythmias and sudden death, cerebrovascular disease, and peripheral arterial disease. Macrovascular complications in patients with diabetes cause an estimated two- to fourfold boosted risk of coronary artery disease, peripheral arterial disease, and cerebrovascular disease. The macrovascular complications of diabetes result from hyperglycemia, excess free fatty acid, and insulin resistance, which cause increased oxidative stress, protein kinase activation, and stimulation of the receptor for advanced glycation end products (factors that act on the endothelium). Additionally, early macrovascular disease is correlated with atherosclerotic plaque in the vasculature supplying the cardiac muscle, brain, limbs, and other organs. Hyperglycemia and hyperinsulinemia hasten atherosclerosis via vascular smooth muscle cell proliferation and inflammation.

Late stages of macrovascular disease encompass complete obstruction of these vessels, which can heighten the risks of myocardial infarction, stroke, claudication, and gangrene. The CDC indicates that 80% of lower limb amputations are the result of diabetes complications, and from 2009 to 2019, the incidence of diabetes-related hospitalizations due to amputation doubled.

Studies show that individuals with T2DM are two to six times more likely to die from a major adverse cardiovascular event. The primary cause of morbidity and mortality in diabetic patients is cardiovascular disease, which accounts for an estimated 52% of deaths in T2DM and 44% in T1DM patients. Additional contributors to the increased cardiovascular risk in persons with diabetes include dyslipidemia, obesity, insulin resistance, inflammation, hypertension, autonomic dysfunction, and diminished vascular responsiveness. Numerous clinical studies have revealed a connection between T2DM and vascular disease, but in nearly all cases other risk factors are present in diabetic patients, such as hypertension, obesity, and dyslipidemia. The American Heart Association indicates that persons with T2DM are two to four times more likely to develop heart failure (HF) compared with those without diabetes, and patients with T2DM and HF tend to have worse clinical outcomes.

Findings from a recent study published in the journal Cell Metabolism revealed that the increasing incidence of pancreatic cancer is closely related to hyperinsulinemia, which is common in individuals with obesity and T2DM. The researchers discovered that hyperinsulinemia directly contributes to pancreatic cancer initiation through insulin receptors in the acinar cells.

Patients should be reminded about the significance of routine healthcare and encouraged to discuss their risk factors for diabetes with their primary healthcare provider. They should also initiate optimal approaches for preventing or reducing modifiable risk factors through medication and lifestyle modifications tailored to patient need.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.