## 2 Classifications of Microvascular and Macrovascular Complications of Diabetes Mellitus
### Classifications of Microvascular Complications of Diabetes Mellitus
#### 2.1.3 Diabetic Nephropathy (DN)  
Diabetes nephropathy (DN) has emerged as a new diabetic consequence as the frequency of diabetes mellitus has increased and diabetes has been diagnosed at a younger age. Approximately 20-40% of type 2 diabetic people will develop DN. As a result, persons with diabetes mellitus who develop DN face increased mortality risks [31].  
Diabetic Nephropathy (DN) Prevalence  
The likelihood of acquiring DN problems in patients who have DM continues to rise; as a result, around 25% of newly diagnosed DM cases will develop diabetic nephropathy, a known DM complication, within a decade. Diabetes mellitus has been established as one of the major causes of chronic kidney disease (CKD), with diabetic nephropathy being one of the leading causes of end-stage renal disease and mortality associated with cardiovascular events and only being detected after a long period of time [32]. Over a decade, around 40% of people with diabetes mellitus will develop DN [33], and finally, roughly 50% of diabetic people will have DN [34].  
Regardless of the medicinal therapies currently available, patients with DN will eventually develop kidney failure [32]. Interestingly, the development and progression of DN are directly associated with poor glycemic management [35], which leads to persistent hyperglycemia, the creation of advanced glycation products (AGEs), and the secretion of inflammatory cytokines [32]. Diabetic nephropathy develops concurrently with other diabetes problems, notably diabetic retinopathy, due to the extended duration of diabetes.  
Diabetic Nephropathy (DN) Pathogenesis  
Although the pathogenesis of DN is not fully and deeply understood, however, increased hyperglyicate states are currently believed to primarily be the culprit in the destruction of renal vasculature, subsequently leading to morphological alterations and, eventually, renal dysfunction [36]. The loss of morphological integrity in the DN includes increased thickness of the glomeruli basement membrane, building up of glomerular mesangial extracellular matrix together with increased collagen depositions, which eventually leads to glomerulosclerosis, inevitably leading to glomerular hyperfiltration and glomerular hypertrophy, elevated excretion of albumin and proteinuria, as well as decreased glomerular filtration rate [36]. Due to the lack of deeper insights into the disease development and progression of DN, as well as the vastness of its pathogenesis, appropriate therapeutic interventions are sorely lacking, and the latter affects patient outcomes [37].  
Some mechanisms involved in the pathogenesis of DN include oxidative stress and inflammatory processes induced by hyperglycemia. In this regard, oxidative stress related to hyperglycemia is believed to play a role in inducing inflammation by facilitating the release of proinflammatory proteins and cytokines. Indeed, some of the inflammatory markers (interleukin-1, IL-6, IL-18, tumor necrosis factor-\(\alpha\)) have been implicated in the development of DN [37]. Therefore, therapeutic approaches targeted at these factors would be more beneficial in the fight against diabetes mellitus, together with its devastating consequences.  
Diabetic Nephropathy (DN) Risk Factors  
The current understanding of DN risk factors concludes that there is an overlap between those involved in diabetic retinopathy (dyslipidemia, hypertension, poor blood glucose control, and sustained active tobacco smoking) and those of DN, and are all classified as modifiable risk factors [36; 38]. However, the same cannot be said for their non-modifiable risk factors; DN non-modifiable risk factors include family history of DN, race (mostly affecting those of African ancestry, American populations with Mexican descent, and Pima people of Native Americans), increasing age, and sex (mainly males) [36; 38].