Practice Essentials
Type 2 diabetes mellitus consists of an array of dysfunctions characterized by
hyperglycemia and resulting from the combination of resistance to insulin
action, inadequate insulin secretion, and excessive or inappropriate glucagon
secretion. See the image below.
Abstract
The pathophysiology of diabetes is related to the levels of insulin within the body, and the body’s ability
to utilize insulin. There is a total lack of insulin in type 1 diabetes, while in type 2 diabetes, the peripheral
tissues resist the effects of insulin. Normally, the pancreatic beta cells release insulin due to increased
blood glucose concentrations. The brain in order for normal functions to occur continually requires
glucose. Hypoglycemia, or low plasma glucose levels, is usually caused by drugs used in the treatment of
diabetes, including insulin and oral antihyperglycemics. The pathophysiology of diabetes involves plasm
concentrations of glucose signaling the central nervous system to mobilize energy reserves. It is based
on cerebral blood flow and tissue integrity, arterial plasma glucose, the speed that plasma glucose
concentrations fall, and other available metabolic fuels. Low plasma glucose causes a surge in autonomic
activity. Diagnosis of hypoglycemia requires verification of low plasma glucose levels. Immediate
treatment is the intake of glucose. The responses to hypoglycemia include decreased insulin secretion,
increased secretion of glucose counter-regulatory hormones such as glucagon and epinephrine, a
greater sympathoadrenal response, related symptoms, and finally, cognitive dysfunction, seizures, or
coma.
Late hypoglycemia of occult diabetes may develop in some patients with impaired glucose tolerance, or
early type 1 or type 2 diabetes. After a high-carbohydrate meal, the patient experiences hypoglycemia.
Neuropathy
The neuropathy stemming from diabetes mellitus has multiple manifestations within the diabetic
foot because it encompasses sensory, motor, and autonomic fibers. Sensory neuropathy affects
small-diameter pain and temperature fibers first, and susceptibility to injury is increased because
these patients are less sensitive to pressure-related trauma and other minor skin injuries
(see Chapter 53). Motor neuropathy affects the longer fibers that innervate the foot, including
intrinsic foot muscles and leg muscles. Atrophy, or muscle wasting, in the intrinsic foot muscles
allows the strong flexor muscles to draw up the toes in a “clawed” position, and new pressure
points emerge at the tips of the toes and the prominent metatarsal heads. Limited joint
mobility and rigidity from glycation of scleral proteins exacerbates the situation by further
changing the normal weight distribution on the foot. Lastly, autonomic neuropathy causes the
skin to become dry through loss of sweat and apocrine gland function. The resulting dry, scaly
skin has a markedly increased susceptibility to skin breakdown and fissures, thus creating a
portal of entry for bacteria. Additionally, diabetic patients can have a blunted neuroinflammatory
response and thus are missing a crucial component of the body’s natural first-line defense against
pathogens.4
Infection
Diabetic patients typically have an altered response to infectious processes owing to defects in
their host immune defense system.5 Moreover, wound healing is delayed in diabetic patients as a
result of abnormal cellular and inflammatory pathways involving fibroblasts, neutrophils,
and advanced glycation end products (AGEs). Glycation is a nonenzymatic chemical reaction
whereby sulfhydryl protein linkages are replaced by glucose, causing impairment in normal
cellular and tissue functions.6 AGEs increase the stiffness of precapillary vessel walls and
contribute to the development of diabetic microangiopathy.7 Additionally, the presence of
neuropathy and ischemia can potentiate the infectious process. The loss of protective sensation
from neuropathy leads to unrecognized injury and secondary infection. Ischemia results in poor
healing, blunts the inflammatory response, and may lead to inadequate tissue levels
of antimicrobial agents.
Ischemia
Much progress has been made in identifying the cause of ischemia in the lower extremities of
diabetic patients, and results have challenged long-standing misconceptions in the literature and
in the medical community at large. It is imperative that practitioners continue to reject the
“small-vessel disease” theory related to occlusions of the microcirculation, as espoused by a
single histologic study in 1959,8 and instead embrace the notion that ischemia results from both
atherosclerotic macrovascular disease and microcirculatory dysfunction.9 Diabetic patients
typically suffer from tibial and peroneal arterial disease with sparing of the foot arteries,
especially the dorsalis pedis and its branches
