**8. Late complications**

for now and the future, some international guidelines recommend early treatment with agents that have complementary mechanism of action. These combinations have benefits related to

The difficulty in getting good metabolic and clinical control of BP in many patients, may result in the development of acute clinical disorders or chronic complications. Physicians must keep in mind when the patient develops acute confusional states or coma; these events could be due to DM *per se*, or other pathologies developed in those patients, such as hepatic failure, renal disease, stroke, respiratory distress, poisoning or drug overdose; the distinction between coma secondary to inadequate level of insulin, and non diabetic disease is crucial for the prognosis

Patients with diabetes are susceptible to four acute metabolic complications: hypoglycemia, ketoacidosis, hyperosmolar and lactic acidosis. All of them can result in coma. The two first are complications of IDDM, while the other two are usually developed in the setting of NIDDM. These clinical situations must be considered completely different from severe disorders that occur not related to DM *per se* such as stroke, acute heart failure, hepatic dysfunction, in others words: *coma* in *diabetic patients* is completely different for *diabetic coma*.

Unfortunately, a lot of patients developed coma situations despite the treatments available, generally caused by incorrect dose, or medication missed dose. This is the relevant point to

*Diabetic ketoacidosis*. It is often caused by cessation of insulin administration but it may result from physical (infection, surgery, traumatism) or emotional stress despite continued insulin therapy. Several complications can be present in diabetic ketoacidosis: erosive gastritis or acute gastric dilatation manifested by pain, vomiting of blood, or weight lost, cerebral edema with or without neurological signs or coma, increased potassium serum (cardiac arrest); myocardial

*Hyperosmolar coma*. This modality of acute diabetes complication is usually due to NIDDM. It is characterized by a profound dehydration resulting from a sustained hyperglycemic diuresis by situations in which the patient is unable to drink enough water to keep up normal urinary excretion of detritus. This situation commonly occurs in elderly patients often living alone or in a nursing home. They develop stroke or bacterial infection that worsens adequate water intake. Hyperosmolar coma can also be caused by peritoneal dialysis or hemodialysis, the use of osmotic agents such as manitol and urea. Clinically, patients show extreme hyperglycemia, hyperosmolality and central nervous system disorders (seizure activity, transient stroke, hemiplegia or clouded sensorium and coma). Pneumonia, gram-negative sepsis or others infections are also very common. Bleeding probably caused by disseminated intravascular coagulation, acute pancreatitis and widespread thrombosis is usually found at necropsy.

compliance, efficacy and safety for the patients.

**7. Acute metabolic complications**

consider other possibilities, and the way is clinical trial.

infarction, respiratory distress syndrome, or thrombosis events.

of the patients.

134 Treatment of Type 2 Diabetes

Diabetic patients are susceptible to developing several complications responsible for morbidity and early mortality; some of them do not present problems, whereas in others, complications appear early, usually after the appearance of the hyperglycemic symptoms developed between 15 and 20 years after the onset of the disease [table 4]. The clinical findings showed the following circulatory abnormalities: atherosclerosis, coronary artery disease, stroke, heart failure, peripheral vascular disease and left ventricular failure.


**Table 4.** Late complications developed in diabetic patients

#### **8.1. Diabetic retinopathy**

Is a relevant cause of blindness; however a high number of diabetic patients never lose the vision. When the occlusion of retinal capillaries occurs, it results in a subsequent formation of saccular and fusiform aneurysm and arteriovenous shunt. Hemorrhages into the inner retinal surface are dot-shaped; conversely, bleeding into the superficial larger nerve fiber produces flame-shaped, blot-shaped or linear lesions. Cotton-wool spots can be observed by angiogra‐ phy, and sudden increase of the number of these lesions has an ominous prognostic sign and is the beginning of rapid progress of retinopathy. Hard exudates are common findings and are probably related to leakage of protein and lipids from damaged capillaries. The lesions must be summarized into two categories: *simple* (microaneurysms, dilated veins, hard exudates, arteriovenous shunts, hemorrhage, cotton-wool spots, increased capillary permeability and capillary closure, and dilation) and *proliferative*: new vessels, vitreous hemorrhage, retinitis proliferans (scar) and retinal detachment.

#### **8.2. Renal disease**

Despite the worldwide importance of diabetic nephropathy as a cause of mortality and morbidity, many questions still remain about treatment aimed at delaying its harmful effects [22, 23]. So far, there is little scientific evidence to support strict glycemic control at this stage, although common sense dictates that wild swings of control should be avoided. Protein restriction may have a role but the studies to support this have not been forthcoming.
