DIABETES

SOWCAR KAREEM JAFFAR#19

PRECEPTOR:DR.ANTHONY TEROSO
  Diabetes mellitus (DM) refers to a group of common
metabolic disorders that share the phenotype of
hyperglycemia.
 DM is the leading cause of end-stage renal disease
(ESRD), nontraumatic lower extremity amputations,
and adult blindness.
DIABETES MELLITUS
INTRODUCTION
  DM is classified on the basis of the pathogenic process
leading to hyperglycemia, as opposed to earlier criteria such
as age of onset or type of therapy

CLASSIFICATION
  Type 1 DM develops as a
result of autoimmunity
against the insulin-producing
Etiologic beta cells, resulting in
complete or near-total insulin
Classification deficiency

of Diabetes  Type 2 DM is a
heterogeneous group of
Mellitus disorders characterized by
variable degrees of insulin
resistance, impaired insulin
secretion, and increased
hepatic glucose production
Etiologic
Classification
of Diabetes
Mellitus
  Maturity-onset diabetes of the young (MODY) and
Etiologic monogenic diabetes are subtypes of DM
characterized by autosomal dominant
Classification inheritance, early onset of hyperglycemia
of Diabetes (usually <25 years; sometimes in neonatal
Mellitus period), and impaired insulin secretion.
 GESTATIONAL DIABETES
 The American Diabetes Association (ADA) recommends that
diabetes diagnosed within the first trimester be classified as
preexisting pregestational diabetes rather than GDM.
 In 2015, the International Diabetes Federation (IDF) estimated that
Etiologic one in seven pregnancies worldwide was affected by either GDM
or preexisting DM.
Classification  Most women with GDM revert to normal glucose tolerance
of Diabetes postpartum but have a substantial risk (35–60%) of developing DM
in the next 10–20 years.
Mellitus  In addition, children born to a mother with GDM also have an
increased risk of developing metabolic syndrome and type 2 DM
later in life.
 Currently, the ADA recommends that women with a history of GDM
undergo lifelong screening for the development of diabetes or
prediabetes at least every 3 years.
  GESTATIONAL DIABETES
 Screening should be performed between 24 and 28 weeks’
gestation in those women not known to have glucose
intolerance earlier in pregnancy. This 50-g screening test is
Etiologic followed by a diagnostic 100-g, 3-hour oral glucose
Classification tolerance test (OGTT) if screening results meet or exceed a
predetermined plasma glucose concentration
of Diabetes  . The risk of fetal malformations is increased 4–10 times in
Mellitus individuals with uncontrolled DM at the time of conception,
and normal plasma glucose during the preconception period
and throughout the periods of organ development in the
fetus should be the goal, with more frequent monitoring of
HbA1c every 2 months throughout gestation.
  The worldwide prevalence of DM has risen dramatically over the
past two decades, from an estimated 30 million cases in 1985 to
415 million in 2017 .
 Based on current trends, the IDF projects that 642 million
individuals will have diabetes by the year 2040.

EPIDEMIOLOGY  The countries with the greatest number of individuals with

diabetes in 2013 are ▪ China (98.4 million) ▪ India (65.1 million) ▪
AND GLOBAL United States (24.4 million) ▪ Brazil (11.9 million) ▪ Russian
Federation (10.9 million)
CONSIDERATION
S
  Up to 80% of individuals with diabetes live in low-income or medium-
income countries.
 Globally, it is estimated that as many of 50% of individuals with diabetes
may be undiagnosed. The prevalence of DM increases with age.
 The prevalence of diabetes is similar among men and women, but

EPIDEMIOLOGY diabetes related mortality rates are higher in men compared to

women.
AND GLOBAL
CONSIDERATIONS
CATEGORIES
OF GLUCOSE
TOLERANCE
CRITERIA FOR
THE
DIAGNOSIS
OF DM
CRITERIA FOR
THE
DIAGNOSIS • The current criteria for the diagnosis of DM emphasize the HbA1c or the FPG as
OF DM the most reliable and convenient tests for identifying DM in asymptomatic
individuals.
  Why is FBS and HBa1c recommended as a use
for screening test for DM?
Widespread use of the FPG or the HbA1c as a screening test for type
2 DM is recommended because
(1) a large number of individuals who meet the current criteria for DM are
■ asymptomatic and unaware that they have the disorder,

SCREENING (2) epidemiologic studies suggest that type 2 DM may be present for up to
a decade before diagnosis,
(3) some individuals with type 2 DM have one or more diabetes-specific
complications at the time of their diagnosis,
(4) treatment of type 2 DM may favorably alter the natural history of DM,
(5) diagnosis of prediabetes should spur efforts for diabetes prevention.
  The ADA recommends screening all
individuals aged >45 years every 3 years and
Screening individuals at an earlier age if they
SCREENING are overweight (BMI >25 kg/m2 or ethnically
relevant definition for overweight) and have
one additional risk factor for diabetes
RISK
FACTORS
FOR TYPE 2
DM
  Insulin is the most important regulator of this metabolic
equilibrium
GLUCOSE
HEMEOSTASIS
reflects a
balance
between hepatic
glucose
production and
peripheral
glucose uptake
and utilization.
GLUCOSE
HEMEOSTASIS
INSULIN
SYNTHESIS

Because C-peptide is cleared more slowly than insulin, it is a useful marker of insulin
secretion and allows discrimination of endogenous and exogenous sources of
insulin in the evaluation of hypoglycemia
  Glucose is the key regulator of insulin secretion by the
pancreatic beta cell.
 Glucose levels >3.9 mmol/L (70 mg/dL) stimulate insulin
synthesis, primarily by enhancing protein translation and
processing.
 Glucose stimulation of insulin secretion begins with its
INSULIN transport into the beta cell by a facilitative glucose
SECRETION transporter GLUT1/2.
 Glucose phosphorylation by glucokinase is the rate-
limiting step that controls glucose-regulated insulin
secretion
INSULIN
SECRETION
 • Glucagon-like peptide-1 (GLP-1) and glucose-dependent
insulinotropic peptide (GIP) are incretin hormones that
bind specific receptors on the beta cell to stimulate insulin
secretion through cyclic AMP production, but have this
effect only when the blood glucose is above the fasting
▪ INSULIN level. Incretin hormones also suppress glucagon
production and secretion
SECRETION:
THE INCRETIN
EFFECT
INSULIN
ACTION
  Type 1 DM is the result of interactions of genetic, environmental, and
immunologic factors that ultimately lead to immune-mediated
destruction of the pancreatic beta cells and insulin deficiency. Type 1
DM can develop at any age, but most commonly develops before 20
years of age.

PATHOGENE
SIS OF TYPE 1
DM
  Risk of developing type 1 DM is increased tenfold in
relatives of individuals with the disease, the risk is
PATHOGENE relatively low: 3–4% if the parent has type 1 DM and 5–
SIS OF TYPE 15% in a sibling (depending on which HLA haplotypes
are shared).
1 DM  Hence, most individuals with type 1 DM (75%) do not
have a first-degree relative with this disorder
  Insulin resistance and abnormal insulin secretion are
central to the development of type 2 DM
PATHOGEN  Type 2 DM has a strong genetic component. The
ESIS OF concordance of type 2 DM in identical twins is between
TYPE 2 DM 70 and 90%. Individuals with a parent with type 2 DM
have an increased risk of diabetes; if both parents
have type 2 DM, the risk approaches 40%
 Type 2 DM is characterized by impaired insulin secretion, insulin
resistance, excessive hepatic glucose production, abnormal fat
metabolism, and systemic low-grade inflammation

PATHOPHYSIO
LOGY:
DIABETES
MELLITUS II
PATHOPHYSIO ▪ Insulin resistance, the decreased ability of insulin to act effectively on
target tissues (especially muscle, liver, and fat), is a prominent feature of
LOGY: type 2 DM and results from a combination of genetic susceptibility and
obesity.
DM TYPE II ▪ Insulin resistance impairs glucose utilization by insulin-sensitive tissues
Metabolic and increases hepatic glucose output; both effects contribute to the
hyperglycemia. ▪ Increased hepatic glucose output predominantly
Abnormalities: accounts for increased FPG levels ▪ Decreased peripheral glucose
utilization results in postprandial hyperglycemia
ABNORMAL  “postreceptor” defects in insulin-regulated
MUSCLE AND phosphorylation/dephosphorylation appear to play the predominant
role in insulin resistance
FAT
Glucose metabolism in insulin-independent
METABOLISM tissues is not altered in type 2 DM.
PATHOPHYSIOL  The obesity accompanying type 2 DM, particularly in a
central or visceral location, is thought to be part of the
OGY: pathogenic process which causes increased levels of
DIABETES circulating free fatty acids and other fat cell products may
MELLITUS II cause insulin resistance in skeletal muscle and liver impair
ABNORMAL FAT glucose utilization in skeletal muscle, promote glucose
production by the liver, and impair beta cell function.
METABOLISM
 In type 2 DM, insulin resistance in the liver reflects the failure
AND of hyperinsulinemia to suppress gluconeogenesis, which
INCREASED results in fasting hyperglycemia and decreased glycogen
HEPATIC storage by the liver in the postprandial state.
PRODUCTION
PATHOPHYSI
OLOGY:
DIABETES
MELLITUS II
INCREASED
LIPID
PRODUCTION
PATHOPHYSI
OLOGY:
DIABETES
MELLITUS II
 ▪ Insulin Resistance Syndromes The insulin resistance
condition comprises a spectrum of disorders, with
hyperglycemia representing one of the most readily
PATHOPHYSI diagnosed features.

OLOGY:
DIABETES
MELLITUS II
INSULIN
RESISTANCE
SYNDROMES
  HISTORY
A complete medical history should be obtained with special emphasis on
DM-relevant aspects such as current weight as well as any recent changes
in weight, family history of DM and its complications, sleep history, risk
factors for cardiovascular disease, exercise, smoking status, history of
pancreatic disease, and ethanol use.
APPROACH Symptoms of hyperglycemia include polyuria, polydipsia, weight loss,
TO THE fatigue, weakness, blurry vision, frequent superficial infections
(vaginitis, fungal skin infections), and slow healing of skin lesions after
PATIENT:DM minor trauma.
In a patient with established DM, the initial assessment should include a
review of symptoms at the time of the initial diabetes diagnosis.
Pregnancy plans should be ascertained in women of childbearing age. The
American Diabetes Association recommends that all women of
childbearing age be counseled about the importance of tight glycemic
control (HbA1c less than 6.5%) prior to conception
  PHYSICAL EXAMINATION:
 In addition to a complete physical examination, special attention
should be given to DM-relevant aspects such as weight and BMI,
retinal examination, orthostatic blood pressure, foot examination,
peripheral pulses, and insulin injection sites.

APPROACH  Blood pressure >130/80 mmHg is considered hypertension in

individuals with diabetes.
TO THE  Because periodontal disease is more frequent in DM, the teeth
PATIENT:DM and gums should also be examined.
 An annual foot examination should (1) assess blood flow (pedal
pulses), sensation ,the ability to sense touch with a monofilament
[5.07, 10-g monofilament], pinprick sensation, ankle reflexes, and
nail care; (2) look for the presence of foot deformities such as
hammer or claw toes and Charcot foot; and (3) identify sites of
potential ulceration.
  The ADA recommends annual screening for distal
symmetric polyneuropathy beginning with the initial
diagnosis of diabetes and annual screening for
autonomic neuropathy 5 years after diagnosis of type
1 DM and at the time of diagnosis of type 2 DM. This
APPROACH testing is aimed at detecting loss of protective
sensation (LOPS) caused by diabetic neuropathy
TO THE
 Diabetes-related eye examination (annual or biannual)
PATIENT:DM
 Diabetes-related foot examination (1–2 times/year by
provider; daily by patient)
 Diabetes-related neuropathy examination (annual)
 Diabetes-related kidney disease testing(annual)
 TYPE 1 DM TYPE 2 DM
 (1) onset of disease prior to
age 30 years;  (1) diabetes onset after the age of
30 years;
 (2) lean body habitus;
APPROACH TO  (3) requirement of insulin as
 (2) are usually obese (80% are
obese, but elderly individuals may
the initial therapy;
THE PATIENT:DM  (4) propensity to develop
be lean);
 (3) may not require insulin therapy
CLASSIFICATION ketoacidosis; and
initially; and
 (4) may have associated conditions
OF DM IN AN  (5) an increased risk of other
autoimmune disorders such as
such as insulin resistance,
hypertension, cardiovascular
INDIVIDUAL autoimmune thyroid disease, disease, dyslipidemia, or polycystic
ovarian syndrome.
adrenal insufficiency,
PATIENT pernicious anemia, celiac  In type 2 DM, insulin resistance is
disease, and vitiligo. often associated with abdominal
obesity (as opposed to hip and thigh
obesity) and hypertriglyceridemia.
  The goals of therapy for type 1 or type 2 diabetes
mellitus (DM) are to
DM  (1) eliminate symptoms related to hyperglycemia,
Management  (2) reduce or eliminate the long-term microvascular
and Therapies and macrovascular complications of DM , and
 (3) allow the patient to achieve as normal a lifestyle as
possible
  The term comprehensive diabetes care to emphasize the fact that optimal
diabetes therapy involves more than plasma glucose management and
medications. Although glycemic control is central to optimal diabetes
therapy, comprehensive diabetes care of both type 1 and type 2 DM should
also detect and manage DM-specific complications, and modify risk factors
for DM-associated diseases. The key elements of comprehensive diabetes
care are summarized

DM
Management
and Therapies
  ■ LIFESTYLE MANAGEMENT IN DIABETES CARE
The American Diabetes Association (ADA) uses the term
DM “Lifestyle Management” to refer to aspects of diabetes care,
Management and including:
Therapies (1) Diabetes self-management education (DSME) and
diabetes self-management support (DSMS);
COMPREHENSIVE (2) Nutrition therapy; and
DIABETES CARE (3) psychosocial care.
 Medical nutrition therapy (MNT)
term used by the ADA to describe the optimal coordination of caloric intake with other
aspects of diabetes therapy (insulin, exercise, and weight loss)

DM
Management
and Therapies
COMPREHENSIVE
DIABETES CARE
  Physical Activity Recommendation
DM ADA recommends 150 min/week (distributed over at
Management least 3 days) of moderate aerobic physical activity
with no gaps longer than 2 days. Resistance exercise,
and Therapies flexibility and balance training, and reduced sedentary
COMPREHEN behavior throughout the day are advised.
SIVE RELATIVE CONTRAINDICATIONS:
DIABETES Untreated proliferative retinopathy
CARE
  To avoid exercise-related hyper- or hypoglycemia,
individuals with type 1 DM should
 (1) monitor blood glucose before, during, and after
exercise;
 (2) delay exercise if blood glucose is >14 mmol/L (250
mg/dL) and ketones are present;
 (3) if the blood glucose is <5.6 mmol/L (100 mg/dL),
COMPREHENSIVE ingest carbohydrate before exercising;
DIABETES CARE  (4) monitor glucose during exercise and ingest
carbohydrate to prevent hypoglycemia;
 (5) decrease insulin doses (based on previous
experience) before and after exercise and inject insulin
into a non exercising area; and
 (6) learn individual glucose responses to different types
of exercise
  Depression, anxiety, or “Diabetes Distress,” defined by
the ADA as “…negative psychological reactions related
PSYCHOSOCIAL to emotional burdens…in having to manage a chronic
disease like diabetes, should be recognized and may
CARE require the care of a mental health specialist.
  The patient’s measurements provide a picture of short-
term glycemic control, whereas the HbA1c reflects
average glycemic control over the previous 2–3 months.
 SMBG is the standard of care in diabetes management
and allows the patient to monitor his or her blood
glucose at any time and The frequency of SMBG
MONITORING measurements must be individualized and adapted to
THE LEVEL OF address the goals of diabetes care.
GLYCEMIC  Measurement of glycated hemoglobin (HbA1c) is the
standard method for assessing long-term glycemic
CONTROL control.
 In patients achieving their glycemic goal, the ADA
recommends measurement of the HbA1c at least
twice per year. More frequent testing (every 3 months)
is warranted when glycemic control is inadequate or
when therapy has changed.
  The target for glycemic control (as reflected by the HbA1c) must
be individualized, and the goals of therapy should be developed
in consultation with the patient after considering a number of
medical, social, and lifestyle issues. The ADA calls this a patient-
centered approach.
ESTABLISHMENT  ADA suggests that the goal is to achieve an HbA1c as close to
OF TARGET normal as possible without significant hypoglycemia

LEVEL OF
GLYCEMIC
CONTROL
  The need for individualized glycemic goals based on
the following general guidelines:
 (1) early in the course of type 2 diabetes when the CVD
risk is lower, improved glycemic control likely leads to
improved cardiovascular outcome, but this benefit may
ESTABLISHMENT occur more than a decade after the period of improved
glycemic control;
OF TARGET
 (2) intense glycemic control in individuals with
LEVEL OF established CVD or at high risk for CVD is not
GLYCEMIC advantageous, and may be deleterious, over a
follow-up of 3–5 years;
CONTROL
 (3) hypoglycemia in such high-risk populations (elderly,
CVD) should be avoided; and
 (4) improved glycemic control reduces microvascular
complications of diabetes even if it does not improve
macrovascular complications like CVD.
  Intensive insulin therapy has the goal of achieving near-normal
glycemia. This approach requires multiple resources, including thorough
and continuing patient education, comprehensive recording of plasma
glucose measurements and nutrition intake by the patient, and a variable
insulin regimen that matches carbohydrate intake and insulin dose.

PHARMACOLOGIC
TREATMENT OF
TYPE 1 DIABETES
  Short-acting insulin analogues should be injected just before (<10 min) and
regular insulin 30–45 min prior to a meal. Sometimes short-acting insulin analogues
are injected just after a meal (gastroparesis, unpredictable food intake).
 In general, individuals with type 1 DM require 0.4–1 units/kg per day of insulin
divided into multiple doses, with ~50% of the insulin given as basal insulin.

PHARMACOLOGIC
TREATMENT OF
TYPE 1 DIABETES
INSULIN
REGIMENS
  The goals of glycemia-controlling therapy for type 2 DM are
similar to those in type 1 DM.
 Whereas glycemic control tends to dominate the management
TYPE 2 DIABETES of type 1 DM, the care of individuals with type 2 DM must also
MELLITUS: include attention to the treatment of conditions associated with
type 2 DM (e.g., obesity, hypertension, dyslipidemia, CVD) and
ESSENTIAL detection/management of DM-related complications .Reduction
ELEMENTS IN in cardiovascular risk is of paramount importance because this is
the leading cause of mortality in these individuals.
COMPREHENSIVE
CARE OF TYPE 2
DIABETES
TYPE 1 AND 2
DIABETES
MELLITUS:
GLUCOSE-
LOWERING
AGENTS
TYPE 1 AND 2
DIABETES
MELLITUS:
GLUCOSE-
LOWERING
AGENTS
  Insulin should be considered as part of the initial
therapy in type 2 DM, particularly in lean individuals
or those with severe weight loss, in individuals with
INSULIN underlying renal or hepatic disease that precludes
oral glucose-lowering agents, or in individuals who
THERAPY IN are hospitalized or acutely ill.
TYPE 2 DM  insulin is usually initiated in a single dose of long-acting
insulin (0.2–0.4 U/kg per day), given in the evening or
just before bedtime (NPH, glargine, detemir, or
degludec
  (1) insulin secretagogues, biguanides, GLP-1 receptor
agonists, and thiazolidinediones improve glycemic
control to a similar degree (1–2% reduction in HbA1c)
and are more effective than α-glucosidase inhibitors,
TYPE 1 AND 2 DPP-IV inhibitors, and SLGT2 inhibitors;
DIABETES  (2) assuming a similar degree of glycemic
MELLITUS: improvement, the clinical advantage of one class of
drugs is not clear; any therapy that improves glycemic
GLUCOSE- control is likely beneficial;
LOWERING  (3) insulin secretagogues, GLP-1 receptor agonists,
AGENTS DPP-IV inhibitors, α-glucosidase inhibitors, and SLGT2
inhibitors begin to lower the plasma glucose
immediately, whereas the glucose-lowering effects of
the biguanides and thiazolidinediones are delayed
by weeks;
  (4) not all agents are effective in all individuals with
type 2 DM;
 (5) biguanides, α-glucosidase inhibitors, GLP-1 receptor
TYPE 1 AND 2 agonists, DPP-IV inhibitors, thiazolidinediones, and
DIABETES SLGT2 inhibitors do not directly cause hypoglycemia;
MELLITUS:  (6) most individuals will eventually require treatment
with more than one class of oral glucose-lowering
GLUCOSE- agents or insulin, reflecting the progressive nature of
LOWERING type 2 DM; and
AGENTS  (7) durability of glycemic control is slightly less for
sulfonylureas compared to metformin or
thiazolidinediones.
  Metformin’s advantages are that it promotes mild weight loss, lowers
insulin levels, and improves the lipid profile slightly. Based on SMBG results
and the HbA1c, the dose of metformin should be increased until the
glycemic target is achieved or maximum dose is reached

Glycemic
management
of type 2
diabetes
  ADA clinical guidelines state that metabolic surgery
SURGICAL should be considered in individuals with type 2 DM and
THERAPIES a body mass index >30 kg/m2 if hyperglycemia is
inadequately controlled despite optimal medical
for DM therapy.
  The most serious complication of therapy for DM is
hypoglycemia.
 Severe, recurrent hypoglycemia warrants examination of
treatment regimen and glycemic goal for the individual patient.
Weight gain occurs with most (insulin, insulin secretagogues,
thiazolidinediones) but not all (metformin, α-glucosidase
ADVERSE inhibitors, GLP-1 receptor agonists, DPP-IV inhibitors) therapies.
EFFECTS OF  If the patient is able and willing, oral treatment with glucose
THERAPY FOR tablets or glucose-containing fluids, candy, or food is
appropriate. A reasonable initial dose is 15–20 g of glucose. If
DM the patient is unable or unwilling (because of neuroglycopenia)
to take carbohydrates orally, parenteral therapy is necessary. IV
administration of glucose (25 g) should be followed by a glucose
infusion guided by serial plasma glucose measurements. If IV
therapy is not practical, SC or IM glucagon (1.0 mg in adults) can
be used, particularly in patients with T1DM.
 DKA and HHS are acute, severe disorders directly related to diabetes. 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
DIABETIC KETOACIDOSIS
Kussmaul respirations and a fruity odor on the patient’s breath
ACUTE (secondary to metabolic acidosis and increased acetone) are classic signs of
the disorder.
DISORDERS
RELATED TO
SEVERE
HYPERGLYCEMIA
ACUTE
DISORDERS
RELATED TO
SEVERE
HYPERGLYCE
MIA
ACUTE
DISORDERS
RELATED TO
SEVERE
HYPERGLYCEMIA
: LABORATORY
VALUES
ACUTE
DISORDERS
RELATED TO
SEVERE
HYPERGLYCEMIA
: MANAGEMENT
OF DKA
  The prototypical patient with HHS is an elderly individual with type 2 DM,
with a several-week history of polyuria, weight loss, and diminished
oral intake that culminates in mental confusion, lethargy, or coma.
ACUTE  Sepsis, pneumonia, and other serious infections are frequent
DISORDERS precipitants and should be sought. In addition, a debilitating condition
(prior stroke or dementia) or social situation that compromises water
RELATED TO intake usually contributes to the development of the disorder.

SEVERE
HYPERGLYCEMIA
HYPERGLYCEMIC
HYPEROSMOLA
R STATE
ACUTE  In both disorders, careful monitoring of the patient’s
fluid status, laboratory values, and insulin infusion rate
DISORDERS is crucial. Underlying or precipitating problems should
RELATED TO be aggressively sought and treated.
SEVERE  A reasonable regimen for HHS begins with an IV insulin
HYPERGLYCEMIA bolus of 0.1 unit/kg followed by IV insulin at a constant
infusion rate of 0.1 unit/kg per hour.
HYPERGLYCEMIC  The insulin infusion should be continued until the
HYPEROSMOLAR patient has resumed eating and can be transferred to a
STATE SC insulin regimen
  The goals of diabetes management during
hospitalization are near-normoglycemia, avoidance of
MANAGEMENT hypoglycemia, and transition back to the outpatient
diabetes treatment regimen.
OF DIABETES  The ADA suggests the following glycemic goals for
IN A hospitalized patients:
HOSPITALIZED (1) in critically or non-critically ill patients: glucose of 7.8–
PATIENT 10.0 mmol/L or 140–180 mg/dL;
(2) in selected patients: glucose of 6.1–7.8 mmol/L or
110–140 mg/dL with avoidance of hypoglycemia
DIABETES Chronic hyperglycemia is the
important etiologic factor leading to
MELLITUS: complications of DM, but the
COMPLICATIO mechanism(s) by which it leads to
such diverse cellular and organ
N dysfunction is unknown
  A summary of the features of diabetes-related
complications includes the following.
 (1) Duration and degree of hyperglycemia correlate
with complications.
DIABETES  (2) Intensive glycemic control is beneficial in all forms
of DM.
MELLITUS:  (3) Blood pressure control is critical, especially in type 2
COMPLICATION DM.
 (4) Survival in patients with type 1 DM is improving, and
diabetes related complications are declining.
 (5) Not all individuals with diabetes develop diabetes-
related complication
  DM is the leading cause of blindness between the ages of 20 and
74 in the United States.
 Duration of DM and degree of glycemic control are the best
predictors of the development of retinopathy; hypertension,
nephropathy, and dyslipidemia are also risk factors.
 Nonproliferative diabetic is marked by retinal vascular
DIABETIC microaneurysms, blot hemorrhages, and cotton-wool spots.

RETINOPATHY  The appearance of neovascularization in response to retinal

hypoxemia is the hallmark of proliferative diabetic retinopathy.
 The most effective therapy for diabetic retinopathy is prevention
 Intensive glycemic and blood pressure control will delay the
development or slow the progression of retinopathy in
individuals with either type 1 or type 2 DM.
 Treatment of proliferative retinopathy or macular edema with laser
photocoagulation and/or anti-VEGF therapy (ocular injection)
usually is successful in preserving vision.
  Diabetic nephropathy is the leading cause of chronic kidney disease
(CKD), ESRD, and CKD requiring renal replacement therapy.
 Albuminuria is a risk factor for cardiovascular disease (CVD) and CKD.
 Diabetic kidney disease refers to albuminuria and reduced GFR (<60
mL/min/1.73 m2 );
 Screening for albuminuria should be performed annually in patients with
type 1 diabetes for ≥5 years, in patients with type 2 diabetes, and
DIABETIC during pregnancy. Albuminuria = spot urinary albumin-to-creatinine
ratio >30 mg/g Cr
NEPHROPATHY Non diabetes-related conditions
that might increase cause
albuminuria are urinary tract
infection, hematuria, heart
failure, febrile illness, severe
hyperglycemia, severe
hypertension, and vigorous
exercise.
  Patients with DM are predisposed to radiocontrast-
induced nephrotoxicity.
 Risk factors for radiocontrast-induced nephrotoxicity
are preexisting nephropathy and volume depletion.
RADIOCONTRAST  Individuals with DM undergoing radiographic
INDUCED procedures with contrast dye should be well hydrated
NEPHROTOXICITY before and after dye exposure, and the serum
creatinine should be monitored for 24–48 h following
the procedure.
 Metformin should be held until postintervention
confirmation of preserved kidney function.
  The optimal therapy for diabetic nephropathy is
prevention by control of glycemia.
 Interventions effective in slowing progression of
albuminuria include
DIABETIC
 (1) improved glycemic control,
NEPHROPATH
 (2) strict blood pressure control, and
Y
 (3) administration of an ACE inhibitor or ARB.
 Dyslipidemia should also be treated.
  The ADA suggests a protein intake of 0.8 mg/kg of
body weight/ day in individuals with diabetic kidney
disease.
DIABETIC  Nephrology consultation should be considered when
NEPHROPATHY albuminuria appears and when the estimated GFR is
less than 30 ml/min per 1.743 m2.
 Referral for transplant evaluation should be made
when the GFR approaches 20 mL/min per 1.743 m2 .
  Diabetic neuropathy, which occurs in ~50% of
individuals with longstanding type 1 and type 2 DM.
 As with other complications of DM, the development
of neuropathy correlates with the duration of
diabetes and glycemic control.
 Additional risk factors are body mass index (BMI) (the
greater the BMI, the greater the risk of neuropathy)
DIABETIC and smoking.
 Distal Symmetric Polyneuropathy (DSPN) DSPN, the
NEUROPATHY most common form of diabetic neuropathy, most
frequently presents with distal sensory loss and pain,
but up to 50% of patients do not have symptoms of
neuropathy
 Annual screening for DSPN should begin 5 years
after diagnosis of type 1 DM and at the time of
diagnosis of type 2 DM and is aimed at detecting loss
of protective sensation (LOPS)
  LOPS and DSPN are major risk factors for foot
ulceration and falls due to small and large nerve fiber
dysfunction.
 Autonomic Neuropathy Individuals with long-standing
type 1 or 2 DM may develop signs of autonomic
DIABETIC dysfunction involving the cholinergic, noradrenergic,
NEUROPATHY and peptidergic (peptides such as pancreatic
polypeptide, substance P, etc.) systems.
 Diabetic polyradiculopathies are usually self-limited
and resolve over 6–12 months.
  Prevention of diabetic neuropathy is critical through
improved glycemic control. Treatment of diabetic
neuropathy is less than satisfactory.
 Patients should be educated that loss of sensation in
the foot increases the risk for ulceration and its
DIABETIC sequelae and that prevention of such problems is
NEUROPATHY paramount.
 Patients with symptoms or signs of neuropathy or
LOPS should check their feet daily and take
precautions (footwear) aimed at preventing calluses or
ulcerations. If foot deformities are present, a podiatrist
should be involved.
  Cardiovascular Disease is increased in individuals with
type 1 or type 2 DM.
 The prognosis for individuals with diabetes who have
coronary artery disease or MI is worse than for
CV nondiabetics.
MORBIDITY AND  CHD is more likely to involve multiple vessels in
MORTALITY individuals with DM.
 In addition to CHD, cerebrovascular disease is increased in
individuals with DM (threefold increase in stroke).
 CABG plus optimal medical management likely has better
outcomes than PCI for individuals with diabetes.
  Aggressive cardiovascular risk modification in all
individuals with DM and glycemic control should be
individualized
 In patients with known CHD and type 2 DM, an ACE
CV inhibitor (or ARB), a statin, and acetylsalicylic acid
(ASA; aspirin) should be considered
MORBIDITY
 The ADA recommends considering the use of aspirin
AND for primary prevention of coronary events in
MORTALITY individuals with diabetes with an increased
cardiovascular risk (>50 years with at least one risk
factor such as hypertension, dyslipidemia, smoking,
family history, or albuminuria)
  If individuals with diabetes have elevated triglyceride
levels (>1.7 mmol/L [150 mg/ dL]) or low HDL
cholesterol (<1 mmol/L [40 mg/dL]) in men and (<1.3
mmol/L [50 mg/dL]) in women,
DYSLIPIDEMIA  lifestyle modification and improved glycemic control
should be further emphasized. If triglycerides remain
>5.7 mmol/L (500 mg/dL), treatment with fish oil and
fibrate drugs may reduce the risk of pancreatitis.
  ADA recommends:
 (1) all patients with diabetes and atherosclerotic
cardiovascular disease should receive high-intensity
statin therapy;
 (2) in patients aged 40–75 years, consider using
moderate-intensity statin therapy (without additional
DYSLIPIDEMIA risk factors) intensity statin therapy (with additional
risk factors);
 (3) in patients <40 years and additional risk
factors,consider moderate-intensity statin therapy.
 The ADA recommendations for individuals with
diabetes who are >75 years are similar to that for
individuals aged 40–75 years.
  In targeting a goal of blood pressure of <140/90
mmHg, therapy should first emphasize lifestyle
modifications such as weight loss, exercise, stress
management, and sodium restriction. The BP goal
should be individualized.
 In some younger individuals or those with increased
CV risk, the provider may target a blood pressure of
HYPERTENSION <130/80 mmHg.
 ADA recommends that all patients with diabetes and
hypertension be treated with an ACE inhibitor or an
ARB initially. Subsequently, agents that reduce
cardiovascular risk (beta blockers, thiazide diuretics,
and calcium channel blockers) should be incorporated
into the regimen.
  DM is the leading cause of nontraumatic lower
extremity amputation in the United States.
 Risk factors for foot ulcers or amputation include male
sex, diabetes for >10 years, peripheral neuropathy,
LOWER abnormal structure of foot (bony abnormalities,
EXTREMITY callus, thickened nails), PAD, smoking, history of
previous ulcer or amputation, visual impairment,
COMPLICATIONS poor glycemic control, and diabetic nephropathy,
especially dialysis.
 Large calluses are often precursors to or overlie
ulcerations.
  The optimal therapy for foot ulcers and amputations is prevention
through identification of high-risk patients, education of the
patient, and institution of measures to prevent ulceration.
 High-risk patients should be identified during the routine, annual
foot examination performed on all patients with DM.
Patient education should emphasize
LOWER (1) careful selection of footwear,
EXTREMITY (2) daily inspection of the feet to detect early signs of poor-fitting
COMPLICATIONS footwear or minor trauma,
(3) daily foot hygiene to keep the skin clean and moist,
(4) avoidance of self treatment of foot abnormalities and high-risk
behavior (e.g., walking barefoot), and
(5) prompt consultation with a health-care provider if an
abnormality arises.
  The most common skin manifestations of DM are
xerosis and pruritus and are usually relieved by skin
moisturizers.
 Diabetic dermopathy, sometimes termed pigmented
pretibial papules, or “diabetic skin spots,” begins as an
DERMATOLOGIC erythematous macule or papule that evolves into an
area of circular hyperpigmentation.
MANIFESTATION  Necrobiosis lipoidica diabeticorum is an uncommon
S disorder, accompanying diabetes in predominantly
young women. This usually begins in the pretibial
region as an erythematous plaque or papules that
gradually enlarge, darken, and develop irregular
margins, with atrophic centers and central ulceration.
They are often painful
  Acanthosis nigricans (hyperpigmented velvety plaques seen on
the neck, axilla, or extensor surfaces) is sometimes a feature of
severe insulin resistance and accompanying diabetes.
 Generalized or localized granuloma annulare (erythematous
plaques on the extremities or trunk),
DERMATOLOGIC  lichen planus (violaceous papules on the cutaneous surface +/–
MANIFESTATION erosions in the mouth and genitalia), and

S  Scleredema (areas of skin thickening on the back or neck at the

site of previous superficial infections) are more common in the
diabetic population.
 Lipoatrophy and lipohypertrophy can occur at insulin injection
sites but are now unusual with the use of human insulin, and
avoided by rotating injection sites
  Long-standing type 1 and 2 DM may affect the motility and
function of the GI and genitourinary systems.
 The most prominent GI symptoms are delayed gastric
emptying (gastroparesis) and altered small- and large-bowel
motility (constipation or diarrhea).
GASTROINTESTI  Erectile dysfunction and retrograde ejaculation are very
NAL common in DM and may be one of the earliest signs of diabetic
neuropathy
/GENITOURINARY  Current treatments for these complications of DM are inadequate
DYSFUNCTION and nonspecific. Improved glycemic control should be a goal, but
has not clearly shown benefit.
 Smaller, more frequent meals that are easier to digest (liquid) and
low in fat and fiber may minimize symptoms of gastroparesis.
 Medications that slow gastric emptying (opioids, GLP-1-receptor
agonists) should be avoided.
  Many common infections are more frequent and severe in the
diabetic population, whereas several rare infections are seen
almost exclusively in the diabetic population.
 Examples of this latter category include rhinocerebral
mucormycosis, emphysematous infections of the gallbladder
and urinary tract, and “malignant” or invasive otitis externa.
 Pneumonia, urinary tract infections, and skin and soft tissue
INFECTIONS infections are all more common in the diabetic population.
 Susceptibility to furunculosis, superficial candidal infections, and
vulvovaginitis are increased. Poor glycemic control is a common
denominator in individuals with these infections.
 Individuals with diabetes have an increased rate of colonization of
S. aureus in the skinfolds and nares. Individuals with diabetes also
have a greater risk of postoperative wound infections.
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