MORPHOLOGY OF DIABETES AND ITS LATE COMPLICATIONS

Pathologic findings in the pancreas are variable and not necessarily dramatic. The important morphologic changes are related to the many late systemic complications of diabetes. There

is extreme variability among patients in the time of onset of these complications, their severity, and the particular organ or organs involved. In individuals with tight control of diabetes,

the onset might be delayed. In most patients, however, morphologic changes are likely to be found in arteries (macrovascular disease), basement membranes of small vessels

(microangiopathy), kidneys (diabetic nephropathy), retina (retinopathy), nerves (neuropathy), and other tissues. These

Figure 24-34Long-term complications of diabetes.

Figure 24-35 A, Insulitis, shown here from a rat (BB) model of autoimmune diabetes, also seen in type 1 human diabetes. (Courtesy of Dr. Arthur Like, University of Massachusetts,

Worchester, MA.) B, Amyloidosis of a pancreatic islet in type 2 diabetes.

Figure 24-36Severe renal hyaline arteriolosclerosis. Note a markedly thickened, tortuous afferent arteriole. The amorphous nature of the thickened vascular wall is evident. (Periodic

acid-Schiff [PAS] stain; courtesy of M.A. Venkatachalam, MD, Department of Pathology, University of Texas Health Science Center at San Antonio, TX.)

Figure 24-37Renal cortex showing thickening of tubular basement membranes in a diabetic patient (PAS stain).

Figure 24-38Electron micrograph of a renal glomerulus showing markedly thickened glomerular basement membrane (B) in a diabetic. L, glomerular capillary lumen; U, urinary space.

(Courtesy of Dr. Michael Kashgarian, Department of Pathology, Yale University School of Medicine, New Haven, CT.)

Figure 24-39Nephrosclerosis in a patient with long-standing diabetes. The kidney has been bisected to demonstrate both diffuse granular transformation of the surface (left) and marked

thinning of the cortical tissue (right). Additional features include some irregular depressions, the result of pyelonephritis, and an incidental cortical cyst (far right).

Figure 24-40Sequence of metabolic derangements leading to diabetic coma in type 1 diabetes mellitus. An absolute insulin deficiency leads to a catabolic state, eventuating in

ketoacidosis and severe volume depletion. These cause sufficient central nervous system compromise to lead to coma and eventual death if left untreated.

TABLE 24-8-- Type 1 Versus Type 2 Diabetes Mellitus (DM)

Type 1 DM Type 2 DM

Clinical Onset: <20 years Onset: >30 years

Normal weight Obese

Markedly decreased blood insulin Increased blood insulin (early);normal to moderate decreased insulin (late)

Anti-islet cell antibodies No anti-islet cell antibodies

Ketoacidosis common Ketoacidosis rare; nonketotic hyperosmolar coma

Genetics 30–70% concordance in twins 50–90% concordance in twins

Linkage to MHC Class II HLA genes No HLA linkage

Linkage to candidate diabetogenic genes (PPARg, calpain 10)

Pathogenesis Autoimmune destruction of b-cells mediated by T cells and humoral

mediators (TNF, IL-1, NO)

Insulin resistance in skeletal muscle, adipose tissue and liver

b-cell dysfunction and relative insulin deficiency

Absolute insulin deficiency

Islet cells Insulitis early No insulitis

Marked atrophy and fibrosis Focal atrophy and amyloid deposition

b-cell depletion Mild b-cell depletion

pertinent clinical, genetic, and histopathologic features that distinguish type 1 and type 2 diabetes.

In both forms, it is the long-term effects of diabetes, more than the acute metabolic complications, that are responsible for the overwhelming proportion of morbidity and mortality. In

most instances, these complications appear approximately 15 to 20 years after the onset of hyperglycemia. Cardiovascular events such as myocardial infarction, renal vascular

insufficiency, and cerebrovascular accidents are the most common causes of mortality in long-standing diabetics. The impact of cardiovascular disease can be gauged from the fact that

it accounts for up to 80% of deaths in type 2 diabetes; in fact, diabetics have a 3 to 7.5 times greater incidence of death from cardiovascular causes compared to the nondiabetic

population[100] ( Fig. 24-41 ). The hallmark of cardiovascular disease is accelerated atherosclerosis of the large and medium-sized arteries (i.e., macrovascular disease). The

pathogenesis of accelerated atherosclerosis involves multiple factors. We have previously

Figure 24-41Incidence of death from cardiovascular causes in diabetic and nondiabetic individuals after a 7-year follow up. MI, myocardial infarction. (Reproduced with permission

from Haffner et al: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without myocardial infarction. N Engl J Med 339:229,

1998.)

Figure 24-42Pancreatic endocrine tumor ("islet cell tumor"). A, The neoplastic cells are monotonous and demonstrate minimal pleomorphism or mitotic activity (H & E stain). B,

Immunoreactivity for insulin confirms the neoplasm is an insulinoma. Clinically, the patient had episodic hypoglycemia.

Date: 2016-04-22; view: 727