Acute Complications of

Diabetes Mellitus
 Acute Complications
Individuals with type 1 or type 2 DM and
severe hyperglycemia (>16.7 mmol/L [300
mg/dL]) should be assessed for clinical
stability, including mentation and hydration.
Diabetic ketoacidosis (DKA) and
hyperglycemic hyperosmolar state (HHS) are
acute, severe disorders directly related to
diabetes.
 DKA and HHS
DKA was formerly considered a hallmark of type 1 DM,
but also occurs in individuals who lack immunologic
features of type 1 DM and who can sometimes
subsequently be treated with oral glucose-lowering
agents
HHS is primarily seen in individuals with type 2 DM.
Both disorders are associated with: absolute or relative
insulin deficiency, volume depletion, and acid-base
abnormalities.
DKA and HHS exist along a continuum of
hyperglycemia, with or without ketosis.
DKA
 DKA
usually develop over 24 h.
DKA results from relative or absolute
insulin deficiency combined with
counterregulatory hormone excess
(glucagon, catecholamines, cortisol, and
growth hormone).
Both insulin deficiency and glucagon
excess, in particular, are necessary for DKA
to develop.
 DKA
The decreased ratio of insulin to glucagon
promotes: gluconeogenesis,
glycogenolysis, and ketone body
formation in the liver, as well as increases in
substrate delivery from fat and muscle (free
fatty acids, amino acids) to the liver.
Markers of inflammation (cytokines, C-
reactive protein) are elevated in both DKA
and HHS.
 DKA
The timely diagnosis is crucial and allows for prompt
initiation of therapy.
Characterized by hyperglycemia, ketosis, and
metabolic acidosis (increased anion gap).
Occasionally, the serum glucose is only minimally
elevated.
Serum bicarbonate is frequently <10 mmol/L, and
arterial pH ranges between 6.8 and 7.3, depending on
the severity of the acidosis.
Serum potassium at presentation may be mildly
elevated, secondary to the acidosis.
 HHS
Usual patients:
elderly individual with type 2 DM
with a several-week history of polyuria
weight loss
diminished oral intake that culminates in mental confusion,
lethargy, or coma.
PE: profound dehydration and hyperosmolality and
reveals hypotension, tachycardia, and altered mental
status.
 HHS
Notably absent are symptoms of nausea,
vomiting, and abdominal pain and the
Kussmaul respirations characteristic of
DKA.
 HHS
Precipitated by a serious, concurrent illness
such as myocardial infarction or stroke.
Sepsis, pneumonia, and other serious
infections are frequent precipitants and should
be sought.
In addition, a debilitating condition (prior
stroke or dementia) or social situation that
compromises water intake usually contributes to
the development of the disorder.
 HHS
Relative insulin deficiency and inadequate
fluid intake are the underlying causes.
Insulin deficiency increases hepatic glucose
production (through glycogenolysis and
gluconeogenesis) and impairs glucose
utilization in skeletal muscle (see above
discussion of DKA).
 HHS
Hyperglycemia induces an osmotic diuresis
that leads to intravascular volume depletion,
which is exacerbated by inadequate fluid
replacement.
The absence of ketosis in HHS is not
understood. Presumably, the insulin deficiency is
only relative and less severe than in DKA.
It is also possible that the liver is less capable of
ketone body synthesis or that the
insulin/glucagon ratio does not favor
ketogenesis.
 HHS
Volume depletion and hyperglycemia are
prominent feature.
Fluid losses and dehydration are usually more
pronounced than in DKA due to the longer
duration of the illness.
 HHS
Fluid replacement should stabilize the
hemodynamic status of the patient (13 L of
0.9% normal saline over the first 23 h).
Because the fluid deficit is accumulated over a
period of days to weeks, the rapidity of
reversal of the hyperosmolar state must balance
the need for free water repletion with the risk
that too rapid a reversal may worsen neurologic
function.
 HHS
After hemodynamic stability is achieved, the IV
fluid administration is directed at reversing the
free water deficit using hypotonic fluids.
A reasonable regimen for HHS begins with an IV
insulin bolus of 0.1 unit/kg followed by IV
insulin at a constant infusion rate of 0.1 unit/kg
per hour.
Chronic complications of DM
 CHRONIC COMPLICATIONS
Microvascular complication
1. Diabetic retinopathy
2. Diabetic retinopathy
3. Diabetic nephropathy
Macrovascular complications
1. Coronary heart disease
2. Peripheral arterial disease
3. Cerebrovascular disease
Nonvascular complications
1. Dermatologic
2. Gastroparesis
 Microvascular
Diabetic retinopathy
1. Nonproliferative-apperas late in the 1st
decade,marked by vascular aneurysms,
blot hemorrhages and cotton wool spots
-pathophysiology includes loss of retinal
pericytes, increased vascular
permeabilityaltered retinal blood flow
leading to ischemia
2.Proliferative- hallmark is the appearance
of neovascularization in response to
retinal ischemia, the newly formed
vessels appear near the optic nerve and
rupture easily leading to vitreal
hemorrhage and retinal detachment.
 Diabetic nephropathy
Is the leading cause of ESRD, it is related
to chronic hyperglycemia, pathogenesis
involves AGEs, hemodynamic alterations
in renal microcirculations and structural
changes in the glomerulus. Causing
microalbuminuria due to renal
hyperperfusion, leading to
macroalbuminuria with decrease in GFR.
 Diabetic neuropathy
Frequently presents with distal sensory
loss, symptoms may include sensation of
numbness, tingling, sharpness,
neuropathic pain develops, as the
neuropathy progresses pain subsides but
a sensory deficit persists in the lower
extremities
 Macrovascular
CHD, PAD & CVD- increased in DM, it
appears to relate to the synergism of
hyperglycemia, individuals with insulin
resistance have high PAI and fibrinogen
w/c enhances coagulation and lowers
fibrinolysis, favoring development of
thrombosis
 Nonvascular
1. Gastrointestinal dysfunction- delayed gastric
emotying and altered bowel motilty caused by
parasympathetic dysfunction secondary to
chronic hyperglycemia
2. Infections-abnormalities in cell mediated
immunity and phagocyte function associated
w/ hyperglycemia. Hyperglycemia aids in the
growth and colonization of a variet of
organisms
3.Dermatologic manifestations
Protracted wound healing and skin
ulccerations. Diabetic dermopathy begins
as erythematous area and evolves to
hyperpigmentation. Acanthosis nigricans is
a feature of insulin resistance