3. What is diabetes?
Diabetes mellitus (DM) refers to a group of
common metabolic disorders that share the
phenotype of chronic hyperglycemia.
Diabetes mellitus may present with
characteristic symptoms such as thirst,
polyuria, blurring of vision, and weight loss.
4. Diabetes
In its most severe forms, ketoacidosis or a non–ketotic
hyperosmolar state may develop and lead to stupor,
coma and, in absence of effective treatment, death.
Often symptoms are not severe, or may be absent, and
consequently hyperglycaemia sufficient to cause
pathological and functional changes may be present
for a long time before the diagnosis is made.
5. Diabetes Long-term Effects
• The long–term effects of diabetes mellitus include
progressive development of the specific complications of :
– retinopathy with potential blindness
– nephropathy that may lead to renal failure
– neuropathy with risk of foot ulcers, amputation
– Charcot joints
– features of autonomic dysfunction, including sexual dysfunction.
• People with diabetes are at increased risk of cardiovascular,
peripheral vascular and cerebrovascular disease
6. • Several distinct types of DM exist and are caused by
a complex interaction of genetics and environmental
factors.
Depending on the etiology of the DM, factors
contributing to hyperglycemia include
reduced insulin secretion,
decreased glucose utilization, and
increased glucose production
8. Types of Diabetes
Classification –on base of the pathologic process
• 1.Type 1 Diabetes Mellitus
• 2.Type 2 Diabetes Mellitus
• 3.Gestational Diabetes
• 4.Other types:
1.LADA (Latent Autoimmune Diabetes in Adults
2.MODY (maturity-onset diabetes of youth)
3.Secondary Diabetes Mellitus
9. Type 1 diabetes
• Was previously called insulin-dependent diabetes mellitus (IDDM) or
juvenile-onset diabetes.
• Type 1 diabetes develops when the body’s immune system destroys
pancreatic beta cells, the only cells in the body that make the
hormone insulin that regulates blood glucose.
• This form of diabetes usually strikes children and young adults,
although disease onset can occur at any age.
• Type 1 diabetes may account for 5% to 10% of all diagnosed cases of
diabetes.
• Risk factors for type 1 diabetes may include autoimmune, genetic,
and environmental factors.
10. Type 2 diabetes
Was previously called non-insulin-dependent diabetes mellitus (NIDDM) or
adult-onset diabetes.
Type 2 diabetes may account for about 90% to 95% of all diagnosed cases of
diabetes.
It usually begins as insulin resistance, a disorder in which the cells do not use
insulin properly. As the need for insulin rises, the pancreas gradually loses its
ability to produce insulin.
Type 2 diabetes is associated with older age, obesity, family history of diabetes,
history of gestational diabetes, impaired glucose metabolism, physical inactivity,
and race/ethnicity.
African Americans, Hispanic/Latino Americans, American Indians, and some
Asian Americans and Native Hawaiians or Other Pacific Islanders are at
particularly high risk for type 2 diabetes.
Type 2 diabetes is increasingly being diagnosed in children and adolescents.
12. Hormones of the Pancreas
• bulk of the pancreas is an exocrine gland
Endocrine pancreas
• Scattered through the pancreas are several hundred thousand clusters of
cells called islets of Langerhans.
• The islets are endocrine tissue containing 4 types of cells.
• In order of abundance, they are the:
• b cells-secrete insulin and amylin;
• a cells- secrete glucagon;
• d cells-secrete somatostatin
• Gamma - cells-secrete a polypeptide of unknown function.
• (36 aa and plays a role in food intake)
13. PATHOGENSIS
• Type 1 DM results from autoimmune beta cell
destruction ultimately leads to insulin deficiency
• At this point, residual functional beta cells still exist
but are insufficient in number to maintain glucose
tolerance.
• Features of diabetes do not become evident until a
majority of beta cells are destroyed (~80%).
14. Pathogenesis & Pathophysiology
• Although other islet cell types
– alpha cells - glucagon-producing
– delta cells - somatostatin-producing
– Gamma cells (PP cells)- pancreatic polypeptide-producing
are spared from the autoimmune process.
15. In summary
• Type 1 – develops with synergetic effect of
1. Genetic predisposition-HLA DR3,DR4
2. Environmental factor- infn-rubela,coxachi
3. Insultis-autoimmune factor
4. Abs-ICA,GAD,IA inflamotory cells-cytokins
5. Beta cell destrustion (80% of beta cells)
16. Type 2 DM
• Insulin resistance and abnormal insulin secretion are central
to the development of type 2 DM
• Type 2 DM has a strong genetic component
• Type 2 DM is characterized by
1. impaired insulin secretion,
2. insulin resistance,
3. excessive hepatic glucose production, and abnormal fat
metabolism.
• Obesity, particularly visceral or central (as evidenced by the
hip-waist ratio), is very common in type 2 DM
17. metabolic syndrome
Central obesity (waist circumference ≥ 94 cm for men
and ≥ 80 cm for women) plus any two of the
following:
1.Triglycerides ≥ 150 mg/dl (1.7 mmol/L)
2.HDL-cholesterol: men < 40mg/dl (1.03 mmol/L),
women < 50mg/dl (1.29 mmol/L)
3. BP ≥ 130/80 mmHg
• 4.Fasting glucose ≥ 100mg/dl (5.6 mmol/L)
18. Type one
• Age
• BMI
• HLA
• Pathogenesis
• Insulin level
• C-peptide
• Complication
• Insulin
requirement
• Hereditary
• Response
to OHA
• Associated
conditions
Type two
• >30 yr
• Usu. obese
• No HLA ,polygenic
• No immune abs .IR
• Partial insulin
deficiency
• Normal/increased
• HHS
• 50%,usu lately
• More common
• 70-90%
• Yes
• Htn , PCOS
CVD,dyslipidemia
<30 yr
Lean body weight
HLA-DR3,DR4 chrom. 6
Auto immune,
immune markers
Complete deficiency
Reduced/none
DKA
All / initially
Less common,
identical twins- 50-70%
No
Other autoimmune disease
19.
20. Insulin Biosynthesis
• Glucose levels > 3.9 mmol/L (70 mg/dL) stimulate insulin synthesis,
• The insulin mRNA is translated as a single chain precursor called
preproinsulin, and removal of its signal peptide during insertion
into the endoplasmic reticulum generates proinsulin.
• Proinsulin consists of three domains: an amino-terminal B chain, a
carboxy-terminal A chain and a connecting peptide in the middle
known as the C peptide.
21. Insulin Biosynthesis
• Within the endoplasmic reticulum, proinsulin is exposed to
several specific endopeptidases which excise the C peptide,
thereby generating the mature form of insulin.
• Insulin and free C peptide are packaged in the Golgi into
secretory granules which accumulate in the cytoplasm.
• C peptide is useful marker of insulin secretion
22. Insulin Secretion
• Glucose is transported into the b cell by facilitated
diffusion through a glucose transporter GLUT2;
• elevated concentrations of glucose in extracellular
fluid lead to elevated concentrations of glucose within
the b cell.
• Elevated concentrations of glucose within the b cell
ultimately leads to membrane depolarization and an
influx of extracellular calcium.
• The resulting increase in intracellular calcium is
thought to be one of the primary triggers for
exocytosis of insulin-containing secretory granules.
23.
24. Action of Insulin on Carbohydrate, Protein and Fat
Metabolism
• Once insulin is secreted into the portal venous system, ~50% is
degraded by the liver.
• Unextracted insulin enters the systemic circulation where it binds to
insulin receptors in target sites.
Carbohydrate
• Facilitates the transport of glucose into muscle and adipose cells –
uptake and utilization
• GLUT4-a tissue specific insulin sensitive glucose transporter
• Facilitates the conversion of glucose to glycogen for storage in the liver
and muscle.
• Decreases the breakdown and release of glucose from glycogen by the
liver
25. Action of Insulin on Carbohydrate, Protein and Fat
Metabolism
Protein
• Stimulates protein synthesis
• Inhibits protein breakdown;
• Diminishes gluconeogenesis
Fat
• Stimulates lipogenesis- the transport of triglycerides to
adipose tissue
• Inhibits lipolysis – prevents excessive production of
ketones or ketoacidosis
26. Gestational diabetes
• A form of glucose intolerance that is diagnosed in some women
during pregnancy.
• During pregnancy, gestational diabetes requires treatment to
normalize maternal blood glucose levels to avoid complications in the
infant.
• After pregnancy, 5% to 10% of women with gestational diabetes are
found to have type 2 diabetes.
• Women who have had gestational diabetes have a 20% to 50%
chance of developing diabetes in the next 5-10 years.
27. Other types of DM
• Other specific types of diabetes result from
specific genetic conditions (such as maturity-
onset diabetes of youth), surgery, drugs,
malnutrition, infections, and other illnesses.
• Such types of diabetes may account for 1% to
5% of all diagnosed cases of diabetes.
28. LADA– T-I in Adults
• Latent Autoimmune Diabetes in Adults (LADA) is a form of
autoimmune (type 1 diabetes) which is diagnosed in
individuals who are older than the usual age of onset of
type 1 diabetes.
• Alternate terms that have been used for "LADA" include
Late-onset Autoimmune Diabetes of Adulthood, "Slow
Onset Type 1" diabetes
• Often, patients with LADA are mistakenly thought to have
type 2 diabetes, based on their age at the time of
diagnosis.
29. LADA– T-I in Adults
• Immune markers for type 1 dm present
• Respond to oral agents in early phase
• Complete beta cell destruction occur at early phase
• Usually lean body weight
30. MODY
MODY – Maturity Onset Diabetes of the Young
MODY is a monogenic form of diabetes with an autosomal dominant
mode of inheritance:
◦ Mutations in any one of several transcription factors or in the enzyme
glucokinase lead to insufficient insulin release from pancreatic ß-cells, causing
MODY.
◦ Different subtypes of MODY are identified based on the mutated gene.
Originally, diagnosis of MODY was based on presence of non-ketotic
hyperglycemia in adolescents or young adults in conjunction with a family
history of diabetes.
However, genetic testing has shown that MODY can occur at any age and
that a family history of diabetes is not always obvious.
34. Prediabetes:
• Prediabetes is a term used to distinguish people who are at
increased risk of developing diabetes. People with prediabetes
have impaired fasting glucose (IFG) or impaired glucose
tolerance (IGT). Some people may have both IFG and IGT.
• IFG is a condition in which the fasting blood sugar level is
elevated (100 to 125 milligrams per decilitre (mg/dL) after an
overnight fast but is not high enough to be classified as diabetes.
• IGT is a condition in which the blood sugar level is elevated (140
to 199 mg/dL after a 2-hour oral glucose tolerance test), but is
not high enough to be classified as diabetes.
35. Prediabetes: Impaired glucose tolerance and impaired
fasting glucose (cont.)
• Progression to diabetes among those with prediabetes is not
inevitable. Studies suggest that weight loss and increased
physical activity among people with prediabetes prevent or
delay diabetes and may return blood glucose levels to normal.
• People with prediabetes are already at increased risk for
other adverse health outcomes such as heart disease and
stroke.
37. Epidemiology
• The worldwide prevalence of DM has risen dramatically
• Based on current trends, >360 million individuals will have
diabetes by the year 2030
• Although the prevalence of both type 1 and type 2 DM is
increasing worldwide, the prevalence of type 2 DM is rising
much more rapidly because of increasing obesity and reduced
activity levels as countries become more industrialized.
38. Epidemology - WHO FACT SHEET
Jan 2011
• More than 220 million people worldwide have diabetes.
• In 2004, an estimated 3.4 million people died from
consequences of high blood sugar.
• More than 80% of diabetes deaths occur in low- and middle-
income countries.
• WHO projects that diabetes deaths will double between 2005
and 2030.
• Healthy diet, regular physical activity, maintaining a normal body
weight and avoiding tobacco use can prevent or delay the onset
of type 2 diabetes.
41. Criteria for the Diagnosis of Diabetes Mellitus
Symptoms of diabetes/polyuria, polydipsia, weight
loss/ plus random blood glucose concentration
11.1 mmol/L (200 mg/dL)
or
• Fasting plasma glucose > 7.0 mmol/L (126 mg/dL)
or
• Two-hour plasma glucose 11.1 mmol/L (200 mg/dL)
during an oral glucose tolerance test
• A1C level of 6.5% or higher.
42. Glucose tolerance
• Glucose tolerance is classified into three categories based on the
FPG
• (1) FPG < 5.6 mmol/L (100 mg/dL) is considered normal
• (2) FPG = 5.6–6.9 mmol/L (100–125 mg/dL) is defined as IFG
• (3) FPG >= 7.0 mmol/L (126 mg/dL) warrants the diagnosis of
DM.
• OGTT
– IGT = 7.8 - 11.1 mmol/L (140 - 199 mg/dL)
– Diabetes = glucose > 11.1 mmol/L (200 mg/dL) 2 h after a 75-g oral
glucose load
43. Screening
• Widespread use of the FPG 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,
(2) epidemiologic studies suggest that type 2 DM may be present for up to a
decade before diagnosis,
(3) as many as 50% of individuals with type 2 DM have one or more diabetes-
specific complications at the time of their diagnosis, and
(4) treatment of type 2 DM may favorably alter the natural history of DM.
The ADA recommends screening all individuals >45 years every 3 years and
screening individuals at an earlier age if they are overweight [body mass index
(BMI) > 25 km/m2] and have one additional risk factor for diabetes
In contrast to type 2 DM, a long asymptomatic period of hyperglycemia is rare
prior to the diagnosis of type 1 DM.
44. Risk Factors - Type 2 Diabetes Mellitus
– Family history of diabetes (i.e., parent or sibling with type 2 diabetes)
– Obesity (BMI > 25 kg/m2)
– Habitual physical inactivity
– Previously identified IFG or IGT
– History of GDM or delivery of baby >4 kg (>9 lb)
– Hypertension (blood pressure >=140/90 mmHg)
– HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level
>250 mg/dL (2.82 mmol/L)
– Polycystic ovary syndrome(pcos) or acanthosis nigricans
– History of vascular disease
45. Prevention or delay of diabetes:
Life style modification
• Research studies have found that lifestyle changes can prevent
or delay the onset of type 2 diabetes among high-risk adults.
• These studies included people with IGT and other high-risk
characteristics for developing diabetes.
• Lifestyle interventions included diet and moderate-intensity
physical activity (such as walking for 2 1/2 hours each week).
• In the Diabetes Prevention Program, a large prevention study of
people at high risk for diabetes, the development of diabetes
was reduced 58% over 3 years.
46. Prevention or delay of diabetes: Medications
• Studies have shown that medications have been successful in preventing
diabetes in some population groups.
• In the Diabetes Prevention Program, people treated with the drug metformin
reduced their risk of developing diabetes by 31% over 3 years.
• Treatment with metformin was most effective among younger, heavier people
• Similarly, in the STOP-NIDDM Trial, treatment of people with IGT with the drug
acarbose reduced the risk of developing diabetes by 25% over 3 years.
• In addition to preventing progression from IGT to diabetes, both lifestyle
changes and medication have also been shown to increase the probability of
reverting from IGT to normal glucose tolerance.
47. Complications of Diabetes Mellitus
-affect many organ and responsible for
majority of morbidity and mortality
-risk of cxn increases as the function of
hyperglycemia
48. Complications of diabetes mellitus
1.Chronic complications /Late Complications/:
-
Vascular-
•Microvascular-
•Macrovascular
Non vascular-
2.Acute complications
-diabetic ketoacidosis / DKA /
-diabetic nonketotic hyperosmolar coma
- Hypoglycemia
50. DM Complications
Macro and Micro vascular complications
Macrovascular Microvascular
CVD
CAD
PAD
Diabetic Retinopathy
Diabetic Nephropathy
Peripheral Neuropathy
PAD
Meltzer et al. CMAJ 1998;20(Suppl 8):S1-S29.
Complications
Erectile Dysfunction
51. Microvascular Complications
• Microvascular complications are specific to diabetes and do not
occur without longstanding hyperglycaemia.
• Other metabolic, environmental and genetic factors are
undoubtedly involved in their pathogenesis.
• Both T1DM and T2DM are susceptible to microvascular
complications, although patients with T2DM are older at
presentation and may die of macrovascular disease before
microvascular disease is advanced.
52. 1.Ophthalmologic Complications of
Diabetes Mellitus
• DM is the leading cause of blindness between the ages of 20 and 74
• Blindness is primarily the result of progressive diabetic retinopathy
and clinically significant macular edema.
• Diabetic retinopathy is classified into two stages:
• 1. Nonproliferative retinopathy
• 2. Proliferative retinopathy
53. 1. Nonproliferative diabetic retinopathy
• is marked by
retinal vascular microaneurysms,
blot hemorrhages, and
cotton wool spots.
• The pathophysiologic mechanisms invoked in nonproliferative
retinopathy include
loss of retinal pericytes,
increased retinal vascular permeability,
alterations in retinal blood flow, and
abnormal retinal microvasculature,
all of which lead to retinal ischemia.
54.
55. 2.Proliferative Retinopathy
• the hallmark of proliferative diabetic retinopathy is
the Neovascularization in response to retinal hypoxia .
• These newly formed vessels appear near the optic nerve
and/or macula and rupture easily, leading to vitreous
hemorrhage, fibrosis, and ultimately retinal
detachment.
• Not all individuals with nonproliferative retinopathy
develop proliferative retinopathy, but the more severe
the nonproliferative disease, the greater the chance of
evolution to proliferative retinopathy within 5 years.
56.
57. DM Retinopathy
• In T1DM background retinopathy is rare before 5 years of
diabetes but its prevalence increases steadily thereafter to
affect over 90% of patients after 20 years.
• After several years of diabetes, the risk of proliferative
changes is about 3% of patients per year, with a cumulative
total of over 60% after 40 years.
• Best predicators for devt of retinopathy
Duration of Dm
Degree of glycemic control
Genetic susceptibility
Hypertension
58. Diabetic retinopathy,
Laser photocoagulation.
• Laser photocoagulation decreases the likelihood of severe
visual loss by over 50% developing in eyes with high risk
proliferative retinopathy.
• The place of photocoagulation in preproliferative chnages is
not yet established.
• Photocoagulation can be used either to destroy specific targets
(e.g. new vessels) or to treat the whole retina (except for the
central macula) –pan retinal photocoagulation.
• The latter reduces overall retinal ischaemia and thus the
stimulus to new vessel formation.
59. Macular edema
• Occur only when NPR present.
• Associated with 25 % chance of moderate
visual loss with in 3 years.
60. 2.Renal Complications of Diabetes Mellitus
• Diabetic nephropathy is the leading cause of ESRD
and a leading cause of DM-related morbidity and
mortality.
• Both microalbuminuria and macroalbuminuria in
individuals with DM are associated with increased risk
of cardiovascular disease.
• Individuals with diabetic nephropathy commonly have
diabetic retinopathy
61. Natural history of diabetic nephropathy
1. Hyperfilteration (incr. GFR) + renal hypertrophy- 1-3 yrs of onset
2. Return to normal GFR(thicking of GBM..) - the 1st 5 yrs
3. Micro albuminurea- appro. 40% of t1dm - after 5-10 yrs
4. Macro albuminurea - > 15 yrs , GFR decline steadily
5. ESRD - >20 yrs
Micro albuminurea=30-300mg/dl in 24 hr urine or
30-300mg albumin to creatine ratio spot collection ) preferable
method
50 % of micro progress to macro albuminurea in next 10 yr
50 % of sb with macroalbuminurea progress to ESRD in next 7-10 yr
62. • Diabetic nephropathy affects 20-40% of patients
with T1DM, particularly those presenting before
puberty and possibly those with an inherited
tendency to hypertension.
• T2DM patients are also susceptible to
nephropathy.
• Over 40% of subjects with T1DM survive more
than 40 years, half of them without developing
significant micro-vascular complications.
63. Nephropathy in T1DM & T2DM
The nephropathy that develops in T2DM differs from that of T1DM in
the following respects:
1. Microalbuminuria or Macroalbuminuria may be present when type
2 DM is diagnosed, reflecting its long asymptomatic period;
2. Hypertension more commonly accompanies microalbuminuria or
macroalbuminuria in type 2 DM;
3. Microalbuminuria may be less predictive of diabetic nephropathy
and progression to macroalbuminuria in type 2 DM.
4. Finally, it should be noted that albuminuria in type 2 DM may be
secondary to factors unrelated to DM, such as hypertension,
congestive heart failure (CHF), prostate disease, or infection
64. Diabetic Nephropathy: Treatment
Interventions effective in slowing progression from
microalbuminuria to macroalbuminuria include:
1. Normalization of glycemia – OHA are CI in advanced Renal
failure, insulin requirement also decrease
2. Strict blood pressure control – target <130/85 if no
micro/macro albumin urea and < 125/75 if present.
3. Administration of ACE inhibitors or ARBs.
4. Dyslipidemia should also be treated.
65. 3.Neuropathy and Diabetes Mellitus
• Diabetic neuropathy occurs in ~50% of individuals with long-
standing type 1 and type 2 DM.
• It may manifest as polyneuropathy, mononeuropathy, and/or
autonomic neuropathy.
• As with other complications of DM, the development of
neuropathy correlates with the duration of diabetes and glycemic
control.
• Additional risk factors are BMI (the greater the BMI, the greater the
risk of neuropathy) and smoking.
• The presence of cardiovascular disease, elevated triglycerides, and
hypertension is also associated with diabetic peripheral neuropathy
66. Polyneuropathy
• The most common form of diabetic neuropathy is distal
symmetric polyneuropathy(DSPN)
• It most frequently presents with distal sensory loss, but up to
50% of patients do not have symptoms of neuropathy.
• Hyperesthesia, paresthesia, and dysesthesia occur.
• Symptoms may include a sensation of numbness, tingling,
sharpness, or burning that begins in the feet and spreads
proximally. GLOVE AND STOCKING PATTERN
• Pain typically involves the lower extremities, is usually
present at rest, and worsens at night . Pain subside and
disappear as it progress but sensory deficit persist.
• P/E- sensory loss(viberation lost first),position sense, loss of
ankle reflex rx-tca,ssri,carbamazepine
67. Polyradiculopathy
• Diabetic polyradiculopathy is a syndrome characterized by severe
disabling pain in the distribution of one or more nerve roots.
• Intercostal or truncal radiculopathy causes pain over the thorax or
abdomen.
• Involvement of the lumbar plexus or femoral nerve may cause
severe pain in the thigh or hip and may be associated with muscle
weakness in the hip flexors or extensors (diabetic amyotrophy).
• Fortunately self limiting over 6-12 moths.
68. Mononeuropathy
• Mononeuropathy (dysfunction of isolated cranial or peripheral
nerves) is less common than polyneuropathy in DM and presents
with pain and motor weakness in the distribution of a single nerve.
• Involvement of the third cranial nerve is most common and is
heralded by diplopia. Physical examination reveals ptosis and
ophthalmoplegia with normal pupillary constriction to light.
• Sometimes other cranial nerves IV, VI, or VII (Bell's palsy) are
affected.
• Peripheral mononeuropathies or simultaneous involvement of more
than one nerve (mononeuropathy multiplex) may also occur
69. Autonomic Neuropathy
• DM-related autonomic neuropathy can involve multiple systems,
including the cardiovascular, gastrointestinal, genitourinary and
metabolic systems. Autonomic neuropathies affecting
• CVS cause a resting tachycardia and orthostatic hypotension.
Reports of sudden death have also been attributed to autonomic
neuropathy.
• GI- Gastroparesis/diarrhea and constipation
• Gus- bladder-emptying abnormalities and sexual dysfunction
• Sudomotor- Hyperhidrosis of the upper extremities and
anhidrosis of the lower extremities result from sympathetic
nervous system dysfunction- dry and cracking skin leads foot ulcer
• Neuroendocrine – reduction in counter regulatory secretion
(glucagon and epinephrine) - reduced hypoglycemic awareness
70. Lower extremity complications
• Foot ulcer and infection cause morbidity and mortality.
• Epidemiology of foot ulcer
• Lifetime risk in t2dm is 15 % and 6% of dm admission are due
to it
• Diabetic foot ulcer is leading cause of non traumatic
amputation.
• Great toe and metatarsophlengeal joint are the commnest
site.
71. Pathogenesis of foot ulcer
• Neuropathy –
• 1. sensory – repeated and sustained trauma (oftentimes
with out the knowledge if the patient) and abnormal
weight bearing (proprioreceptor disorder) during walking
• 2.motor – abnormal foot mechanics(deformity ) claw and
hammer toe and charcots joint
• 3. autonomic – dry ,anhidrosis and cracked skin (fissure)
all this leads to ulceration
• Peripheral vascular disorder-
poor wound healing and gangrene leading to infection
72. Risk factors for foot ulcer
• male smoking infections
DM >10 yrs hx of ulceration or amputation
• poor glycemic control
• PVD visual impairment
• PN
• Foot deformity (callus,thick nail)
73. P/E of diabetic foot
• Inspection –foot deformity ,fissure, toe nails
ulcer(blister)
• Palpation- Temp,capilary filling,sensory exam
• DTR,ankle /brachial SBP index
• IX- doppler uls ,xray,bone scan
74.
75. Grade 0 is no ulcer but a
high risk foot.
this as a patient with pre-
ulcerative lesions, healed
ulcers, or the presence of a
bony deformity.
76. Grade 1 is a superficial ulcer
involving the full skin thickness
but not the underlying tissues.
It does not extend into the
subcutaneous tissue.
77. A Grade 2 ulcer is a deep ulcer extending
through the subcutaneous tissue. It may
expose bone, tendon, or ligaments but
does not involve the underlying bone or an
abscess.
78. The Grade 3 ulcer is a deep ulcer
involving cellulitis or abscess and
often osteomyelitis.
79. Grade 4 ulcer is one with gangrene of a
digit or localized gangrene, and
80. The Grade 5 ulcer
involves gangrene of the
foot. It requires
disarticulation
82. Infections
• In Dm patients has greater freq and severity of infections---
b/se CMI abn& phagocyosis fun also impaired by
hyperglycemia, reduced vasularity and hyperglycemia aids
colonization
• Many common infn become frequent (UTI,pnemonia,skinand
soft ts inf)
• Etiologies are the same as the general population but Gr-ve
,s.aures and M.tb are also common
• Complication of UTI- emphysematous pyelonephritis/cystis
• Frunculosis, superficial candidal infections,vulvovaginatis
• Post op wound infection
89. Diabetic dermopathy (diabetic skin
spots)pegimented pretibial papules
• Diabetic Dermopathy Also known
as shin spots, most common
cutaneous finding in diabetics
(approximately 50% of diabetics).
• Round to oval atrophic
hyperpigmented lesions on the
pretibial areas of the lower
extremities.
90. • Asymptomatic, resolve spontaneously
leaving a scar usually following
improved blood glucose control. Usually
occurs in older diabetic patients who
have had diabetes >10 years. Occurs
more frequently in diabetic patients
with retinopathy, neuropathy, and
nephropathy. Can be indicator of poor
control of blood glucose levels.
• Early lesions usually raised, then flatten.
• Brownish hyperpigmentation due to
hemosiderin deposits. Occur bilateral
with asymmetrical distribution.
91. Acanthosis Nigricans
• Hyperpigmentation and thickening of epidermis Precedes
diabetes, considered a marker for the disease,
• most common in overweight diabetic patients.
• Usually occurs in skin folds, often described as velvety Neck,
back, axillae, groin region, over joints in the hands/feet.
• thought to be a manifestation of insulin resistance, high
concentrations of insulin may stimulate growth factor
receptors on keratinocytes promoting epidermal cell
proliferation.
92.
93. Necrobiois lipodium diabeticorum
• Degenerative disease of collagen in the
dermis and subcutaneous fat with an
atrophic epidermis.
• Precedes onset of diabetes in 15-20% of
patients Lesions progress to ulcers if
predisposed to trauma Location:
• 85% anterior aspect-pretibial region of
lower extremeties, 15% hands,
forearms, face, scalp
94. Eruptive Xanthomas
• Occur in hyperlipidemic/hyperglycemic states: uncontrolled
diabetic patients. Most common in young men with Type 1
diabetes Resistance to insulin makes it difficult for the body to
clear the fat from the blood.
• Eruptive Xanthomas Usually asymptomatic firm, waxy, yellow
papules in the skin. Enlargements can have erythematous
halo, can itch. Occurs most often on the back of hands/feet,
arms/legs, buttocks, face-eyes.
95. • Eruptive Xanthomas Increase risk
of developing pancreatitis.
Eruptions can resolve in a few
weeks with
hyperlipidemic/hyperglycemic
control, lipid lowering
medications.
96. Macro vascular cxn
• CHF,PAD,CAD,MI,SUDDEN DEATH- 1-5 X FOLD WITH DM
• Stroke Is 3x fold in dm.
• Dm is major RF for CVD(like htn,smoking,dyslipedimia)
• Screen Dm pts for CHD if
SX of ischemia
PAD/carotid AD
Resting ECGindicate prior MI
Ptn urea
Plan to initiate exercise program
• MI in dm – more worse(mutiple vessels may be affected)
• -silent ischemia is common
97. • Risk factors for development of macrovascular cxn in
dm are htn,dyslipedmia,smoking,obesity,physical
inactivity ,micro/macro albumin..
• Rx – glycemic control controversial
• Other RF modification
• ACEi,Bblocker,ASA dyslipedmia rx
99. Acute Complications of DM
• Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar
state (HHS) are acute complications of diabetes.
• DKA was formerly considered a hallmark of type 1 DM, but it
also occurs in individuals who lack immunologic features of
type 1 DM
• 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.
100. Manifestations of Diabetic Ketoacidosis
Diabetic ketoacidosis signs and symptoms often develop quickly,
sometimes within 24 hours.
• Excessive thirst -- polydipysia
• Frequent urination-- polyuria
• Nausea and vomiting
• Abdominal pain
• Loss of appetite
• Weakness or fatigue
• Shortness of breath
• Fruity-scented breath
• Confusion
• High blood sugar level
• High ketone level in urine
• Kassmaul respiration– deep & fast
• Metabolic acidosis
101. Causes & pathophysiology of DKA
• 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.
• 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
102. Causes & pathophysiology of DKA
• An illness. An infection or other illness
• Missed insulin treatments or inadequate insulin therapy
• Stress
• Physical or emotional trauma
• High fever
• Surgery
• Heart attack
• Stroke
• Alcohol or drug abuse
103. Mx of Diabetic Ketoacidosis
• Confirm diagnosis ( plasma glucose, positive serum ketones,
metabolic acidosis).
• Admit to hospital; intensive-care setting may be necessary for
frequent monitoring or if pH < 7.00 or unconscious.
• Assess:
• Serum electrolytes (K+, Na+, Mg2+, Cl-, bicarbonate,
phosphate)
• Acid-base status—pH, HCO3-, PCO2, b-hydroxybutyrate
• Renal function (creatinine, urine output)
• Replace fluids: 2–3 L of 0.9% saline over first 1–3 h (10–15
mL/kg per hour); subsequently, 0.45% saline at 150–300
mL/h; change to 5% glucose and 0.45% saline at 100–200
mL/h when plasma glucose reaches 250 mg/dL (14 mmol/L).
104. Mx of Diabetic Ketoacidosis
• Administer short-acting insulin: IV (0.1 units/kg) or IM (0.3 units/kg), then 0.1
units/kg per hour by continuous IV infusion; increase 2- to 3-fold if no response by
2–4 h. If initial serum potassium is < 3.3 mmol/L (3.3 meq/L), do not administer
insulin until the potassium is corrected to > 3.3 mmol/L (3.3.meq/L).
• Assess patient: What precipitated the episode (noncompliance, infection, trauma,
infarction, cocaine)? Initiate appropriate workup for precipitating event (cultures,
CXR, ECG).
• Measure capillary glucose every 1–2 h; measure electrolytes (especially K+,
bicarbonate, phosphate) and anion gap every 4 h for first 24 h.
• Monitor blood pressure, pulse, respirations, mental status, fluid intake and output
every 1–4 h.
• Replace K+: 10 meq/h when plasma K+ < 5.5 meq/L, ECG normal, urine flow and
normal creatinine documented; administer 40–80 meq/h when plasma K+ < 3.5
meq/L or if bicarbonate is given.
• Continue above until patient is stable, glucose goal is 150–250 mg/dL, and acidosis
is resolved. Insulin infusion may be decreased to 0.05–0.1 units/kg per hour.
• Administer intermediate or long-acting insulin as soon as patient is eating. Allow
for overlap in insulin infusion and subcutaneous insulin injection.
105. Hyperglycemic Hyperosmolar State
Clinical Features
• An elderly individual with type 2 DM,
• With a several week history of polyuria, weight loss, and
diminished oral intake
• Mental confusion, lethargy, or coma.
• Profound dehydration and hyperosmolality and reveals
hypotension, tachycardia, and altered mental status.
• HHS is often precipitated by a serious, concurrent illness such
as myocardial infarction or stroke, Sepsis, pneumonia
106. Pathophysiology
• Relative insulin deficiency and inadequate fluid intake are the
underlying causes of HHS.
• Insulin deficiency increases hepatic glucose production
(through glycogenolysis and gluconeogenesis) and impairs
glucose utilization in skeletal muscle
• 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 completely understood.
Presumably, the insulin deficiency is only relative and less
severe than in DKA.
• Lower levels of counterregulatory hormones and free fatty
acids have been found in HHS than in DKA
107. Laboratory Abnormalities and Diagnosis of
HHS
• Marked hyperglycemia [plasma glucose may be >55.5
mmol/L (1000 mg/dL)],
• Hyperosmolality (>350 mosmol/L),
• Prerenal azotemia.
• In contrast to DKA, acidosis and ketonemia are absent or
mild.
• A small anion gap metabolic acidosis may be present
secondary to increased lactic acid.
• Moderate ketonuria, if present, is secondary to
starvation
114. 2. Glucose balance and Glucose counter
regulation
Glucose is –
Obligate metabolic fuel for brain
Brain can’t store glucose except for few
minutes in the form of glycogen
Brain requires continuous supply of glucose
114
115. Balance and Counter regulation
• Plasma glucose level 70-110 mg% /3.9 -
6.1mmol/L
• Transient variations
- After meals, Exercise, etc
• Between meals and during fasting states
– Endogenous glucose production
– Hepatic glycogenolysis
– Hepatic and renal gluconeogenesis
115
117. Balance and Counter regulation
Gluconeogenesis - requires precursors :
• From muscle and adipose tissue
To liver and kidneys
• Muscle provides –
- lactate, pyruvate, alanine, glutamine,
and other amino acids
• Adipose tissue provides -
– Triglycerides which are converted into
– Fatty acids and Glycerol
117
118. Balance and Counter regulation
• Fatty acids are fuel to tissues in glucose
shortage
• Brain does not use Fatty acids
• uses only glucose
118
119. Balance and Counter regulation
Systemic glucose balance is maintained
• Network of hormones
• Neural signals
• Substrate effects
119
120. Balance and Counter regulation
When plasma glucose level declines
– Insulin plays dominant role
• Its production decreases
• Hepatic glycogenolysis increases
• Hepatic and renal gluconeogenesis increases
120
121. Balance and Counter regulation
Low insulin level
• Reduces glucose utilization in peripheral tissue
• Induces lipolysis from adipose tissue
• Induces proteolysis from muscle
• Decreased insulin production = 1st defense
against hypoglycemia
121
122. Balance and Counter regulation
Plasma glucose level below
physiologic range
• Counter regulatory hormones released
• Glucagon = 2nd defense against hypo
• Stimulates hepatic glycogenolysis
• Produced in alpha cells of pancreas
122
123. Balance and Counter regulation
Epinephrine from adrenal medulla
• Stimulates hepatic glycogenolysis
• Stimulates hepatic and renal gluconeogenesis
• Epinephrine = 3rd defense against
hypoglycemia
123
124. Defense against Hypo
• 1. decrease insulin production
• 2. glucagon production
• 3. Epinephrine
• 4.cortisol & GH
124
125. Balance and Counter regulation
When hypoglycemia is prolonged
• Cortisol and Growth hormone get involved
• Support glucose production
• Limit glucose utilization in peripheral tissue
125
128. Clinical manifestations con’t
Signs of hypoglycemia during sleep
• Crying out
• Having nightmares
• Pajamas or sheets damp from perspiration
• Feeling tired, irritable, confused after
waking up
128
129. 4. Hypoglycemia in Diabetes
• Limiting factor in treatment of DM
• Recurrent morbidity in T1DM
• Less common in T2DM
• Sometimes fatal
• Metformin = No hypoglycemia effect
• Metformin + Sulphonylureas = Hypo
• Metformin + Insulin = Hypo – same as insulin
alone in T1DM
129
130. Conventional Risk Factors for Hypo
• (1) insulin (or insulin secretagogue) doses are excessive, ill-timed, or
of the wrong type;
• (2) the influx of exogenous glucose is reduced (e.g., during an
overnight fast or following missed meals or snacks);
• (3) insulin-independent glucose utilization is increased (e.g., during
exercise);
• (4) sensitivity to insulin is increased (e.g., with improved glycemic
control, in the middle of the night, late after exercise, or with
increased fitness or weight loss);
• (5) endogenous glucose production is reduced (e.g., following
alcohol ingestion);
• (6) insulin clearance is reduced (e.g., in renal failure).
130
132. Defective Glucose Counterregulation
During aggressive insulin therapy of DM In the setting of
endogenous insulin deficiency
insulin levels do not decrease as plasma glucose levels
fall;
the first defense against hypoglycemia is lost.
Furthermore, because the decrement in intraislet insulin
is normally a signal to stimulate glucagon secretion,
glucagon levels do not increase as plasma glucose levels
fall further;
the second defense against hypoglycemia is lost.
132
133. Defective Glucose Counterregulation
Finally, the increase in epinephrine levels, the third defense
against hypoglycemia, in response to a given level of
hypoglycemia is typically attenuated.
The glycemic threshold for the sympathoadrenal
(adrenomedullary epinephrine and sympathetic neural
norepinephrine) response is shifted to lower plasma glucose
concentrations.
That is typically the result of recent antecedent iatrogenic
hypoglycemia. In the setting of absent decrements in insulin and
of absent increments in glucagon, the attenuated increment in
epinephrine causes the clinical syndrome of defective glucose
counterregulation
133
134. Hypoglycemia Unawareness
• The attenuated sympathoadrenal response to
hypoglycemia causes the clinical syndrome of
hypoglycemia unawareness,
• loss of the warning adrenergic and cholinergic
symptoms that previously allowed the patient
to recognize developing hypoglycemia and
therefore abort the episode by ingesting
carbohydrates
134
139. Treatment con’t
If unable to take orally
• I.V. glucose,
• Then continue glucose infusion
• If I.V. glucose not practical
• Glucagon 1.0 mg S/C or I.M. for adults
- Not effective – Liver glycogen depleted
139
140. 7. Prevention
• Understand hypoglycemia mechanism
• Avoid offending Drugs or Reduce dose
• Treat underlying illnesses/ insulinoma,etc/
• If low or absent – Replace Cortisol + GH
• Avoid or minimize all causes of
hypoglycemia
140
141. Prevention con’t
• Diabetes medication schedule
• Understand which drugs cause hypo
• Meal plan
• Daily activity
– Check BS before Sports, Exercise
– Take snack if <100 mg%
– Additional tests as needed
• Alcohol beverage
• Empty stomach
• DM management plan
141
144. Management of DM
• The major components of the treatment of
diabetes are:
• Diet and Exercise
A
• Oral hypoglycaemic
therapy
B
• Insulin Therapy
C
145.
146.
147.
148. A. Diet
Diet is a basic part of management in every case.
Treatment cannot be effective unless adequate
attention is given to ensuring appropriate nutrition.
Dietary treatment should aim at:
◦ ensuring weight control
◦ providing nutritional requirements
◦ allowing good glycaemic control with blood glucose levels
as close to normal as possible
◦ correcting any associated blood lipid abnormalities
149. A. Diet (cont.)
The following principles are recommended as dietary guidelines for people with
diabetes:
Dietary fat should provide 25-35% of total intake of calories but saturated fat
intake should not exceed 10% of total energy. Cholesterol consumption should be
restricted and limited to 300 mg or less daily.
Protein intake can range between 10-15% total energy (0.8-1 g/kg of desirable
body weight). Requirements increase for children and during pregnancy. Protein
should be derived from both animal and vegetable sources.
Carbohydrates provide 50-60% of total caloric content of the diet. Carbohydrates
should be complex and high in fibre.
Excessive salt intake is to be avoided. It should be particularly restricted in people
with hypertension and those with nephropathy.
150. Exercise
Physical activity promotes weight reduction and improves
insulin sensitivity, thus lowering blood glucose levels.
Together with dietary treatment, a programme of regular
physical activity and exercise should be considered for each
person. Such a programme must be tailored to the
individual’s health status and fitness.
People should, however, be educated about the potential
risk of hypoglycaemia and how to avoid it.
151. B. Oral Anti-Diabetic Agents
• There are currently four classes of oral anti-
diabetic agents:
i. Biguanides
ii. Insulin Secretagogues – Sulphonylureas
iii. Insulin Secretagogues – Non-sulphonylureas
iv. α-glucosidase inhibitors
v. Thiazolidinediones (TZDs)
153. B.1 Oral Agent Monotherapy
If glycaemic control is not achieved (HbA1c > 6.5% and/or;
FPG > 7.0 mmol/L or; RPG >11.0mmol/L) with lifestyle
modification within 1 –3 months, ORAL ANTI-DIABETIC
AGENT should be initiated.
In the presence of marked hyperglycaemia in newly
diagnosed symptomatic type 2 diabetes (HbA1c > 8%, FPG
> 11.1 mmol/L, or RPG > 14 mmol/L), oral anti-diabetic
agents can be considered at the outset together with
lifestyle modification.
154. B.1 Oral Agent Monotherapy (cont.)
As first line therapy:
Obese type 2 patients, consider use of metformin, acarbose or TZD.
Non-obese type 2 patients, consider the use of metformin or insulin
secretagogues
Metformin is the drug of choice in overweight/obese patients. TZDs and acarbose
are acceptable alternatives in those who are intolerant to metformin.
If monotherapy fails, a combination of TZDs, acarbose and metformin is
recommended. If targets are still not achieved, insulin secretagogues may be
added
155. B.2 Combination Oral Agents
Combination oral agents is indicated in:
• Newly diagnosed symptomatic patients with
HbA1c >10
• Patients who are not reaching targets after 3
months on monotherapy
156. B.3 Combination Oral Agents and Insulin
If targets have not been reached after optimal dose of combination therapy for 3
months, consider adding intermediate-acting/long-acting insulin (BIDS).
Combination of insulin+ oral anti-diabetic agents (BIDS) has been shown to
improve glycaemic control in those not achieving target despite maximal
combination oral anti-diabetic agents.
Combining insulin and the following oral anti-diabetic agents has been shown to
be effective in people with type 2 diabetes:
◦ Biguanide (metformin)
◦ Insulin secretagogues (sulphonylureas)
◦ Insulin sensitizers (TZDs)(the combination of a TZD plus insulin is not an approved indication)
◦ α-glucosidase inhibitor (acarbose)
Insulin dose can be increased until target FPG is achieved.
158. General Guidelines for Use of Oral Anti-Diabetic Agent
inDiabetes
In elderly non-obese patients, short acting insulin secretagogues can be started
but long acting Sulphonylureas are to be avoided. Renal function should be
monitored.
Oral anti-diabetic agent s are not recommended for diabetes in pregnancy
Oral anti-diabetic agents are usually not the first line therapy in diabetes
diagnosed during stress, such as infections. Insulin therapy is recommended for
both the above
Targets for control are applicable for all age groups. However, in patients with co-
morbidities, targets are individualized
When indicated, start with a minimal dose of oral anti-diabetic agent, while
reemphasizing diet and physical activity. An appropriate duration of time (2-16
weeks depending on agents used) between increments should be given to allow
achievement of steady state blood glucose control
159. C. Insulin Therapy
A.Short-term use:
Acute illness, surgery, stress and emergencies
Pregnancy
Breast-feeding
Insulin may be used as initial therapy in type 2 diabetes
in marked hyperglycaemia
Severe metabolic decompensation (diabetic ketoacidosis, hyperosmolar
nonketotic coma, lactic acidosis, severe hypertriglyceridaemia)
B.Long-term use:
If targets have not been reached after optimal dose of combination therapy or
BIDS, consider change to multi-dose insulin therapy. When initiating this,insulin
secretagogues should be stopped and insulin sensitisers e.g. Metformin or TZDs,
can be continued.
160. Insulin regimens
The majority of patients will require more than one daily injection if good
glycaemic control is to be achieved. However, a once-daily injection of an
intermediate acting preparation may be effectively used in some patients.
Twice-daily mixtures of short- and intermediate-acting insulin is a commonly
used regimen.
In some cases, a mixture of short- and intermediate-acting insulin may be given
in the morning. Further doses of short-acting insulin are given before lunch and
the evening meal and an evening dose of intermediate-acting insulin is given at
bedtime.
Other regimens based on the same principles may be used.
A regimen of multiple injections of short-acting insulin before the main meals,
with an appropriate dose of an intermediate-acting insulin given at bedtime, may
be used, particularly when strict glycaemic control is mandatory.
163. Self-Care
Patients should be educated to practice self-care. This allows
the patient to assume responsibility and control of his / her
own diabetes management. Self-care should include:
◦ Blood glucose monitoring
◦ Body weight monitoring
◦ Foot-care
◦ Personal hygiene
◦ Healthy lifestyle/diet or physical activity
◦ Identify targets for control
◦ Stopping smoking
