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Diabetes Mellitus


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Title: Diabetes Mellitus

Diabetes Mellitus
  • Diabetes mellitus (DM) is a syndrome of chronic
    hyperglycemia due to relative insulin deficiency,
    resistance, or both.
  • Epidemiology
  • The prevalence of diabetes for all age groups
    worldwide was estimated to be 2.8 in 2000 and to
    increase to 4.4 in 2030.
  • At diagnosis, 50 of patients have micro-vascular
    complications (diabetic neuropathy, nephropathy,
    or retinopathy).
  • The risk of macro-vascular complications is at
    least two times higher than that of the general

  • The risk of developing diabetes increases with
    age, obesity, and lack of physical activity.
  • Type 2 diabetes is more common in individuals
    with a family history of the disease.
  • It is more common in women with prior history of
    gestational diabetes and polycystic ovarian
    syndrome and in individuals with hypertension,
    dyslipidemia or impaired glucose tolerance.

Insulin structure and secretion
  • Insulin is the key hormone involved in the
    storage and controlled release within the body of
    the chemical energy available from food.
  • It is coded for on chromosome 11 and synthesized
    in the beta-cells of the pancreatic islets as a
    polypeptide hormone.
  • After secretion, insulin enters the portal
    circulation and is carried to the liver, its
    prime target organ. About 50 of secreted insulin
    is extracted and degraded in the liver the
    residue is broken down by the kidneys. C-peptide
    is only partially extracted by the liver (and
    hence provides a useful index of the rate of
    insulin secretion).

  • glucose metabolism
  • Blood glucose levels are closely regulated in
    health within the range of 3.5-8.0 mmol/L (63-144
    mg/dL), despite the varying demands of food,
    fasting and exercise.
  • The principal organ of glucose homeostasis is the
    liver, which absorbs and stores glucose (as
    glycogen) in the post-absorptive state and
    releases it into the circulation between meals to
    match the rate of glucose utilization by
    peripheral tissues.
  • The liver by the process of gluconeogenesis can
    form new glucose from end metabolites of fat ,
    protein, and lactic acid.
  • Glucose production
  • About 200 g of glucose is produced and utilized
    each day. More than 90 is derived from liver
    glycogen and hepatic guconeogenesis, and the
    remainder from renal gluconeogenesis.

  • Glucose utilization
  • The brain is the major consumer of glucose. Its
    requirement is 1 mg/kg bodyweight per minute, or
    100 g daily in a 70 kg man.
  • Glucose uptake by the brain is obligatory and is
    not dependent on insulin, and the glucose used is
    oxidized to carbon dioxide and water.
  • Other tissues, such as muscle and fat, are
    facultative glucose consumers.
  • Glucose taken up by muscle is stored as glycogen
    or broken down to lactate, which re-enters the
    circulation and becomes a major substrate for
    hepatic gluconeogenesis. But the main source of
    muscle energy is derived from fatty-acid
  • Fat tissue used glucose as a source of energy and
    as a substrate for triglyceride synthesis
    lipolysis releases fatty acids from triglyceride
    together with glycerol, another substrate for
    hepatic gluconeogenesis.

Principal actions of insulin
  • Rapid (seconds)
  • Increased transport of glucose, amino acids, and
    K into insulin-sensitive cells
  • Intermediate (minutes)
  • Stimulation of protein synthesis Inhibition of
    protein degradation
  • Activation of glycolytic enzymes and glycogen
  • Inhibition of phosphorylase and gluconeogenic
  • Delayed (hours)
  • Increase in mRNAs for lipogenic and other enzymes

  • Hormonal regulation
  • Insulin actions in the fasting and postprandial
    states differ . In the fasting state its main
    action is to regulate glucose release by the
    liver, and in the postprandial state it
    additionally facilitates glucose uptake by fat
    and muscle.
  • The effect of counter-regulatory hormones
    (glucagon, epinephrine (adrenaline), cortisol and
    growth hormone) is to cause greater production of
    glucose from the liver and less utilization of
    glucose in fat and muscle for a given level of

  • Glucose transport
  • Cell membranes are not inherently permeable to
  • A family of specialized glucose-transporter
    (GLUT) proteins carry glucose through the
    membrane into cells.
  • These are glycoproteins, coded for on the short
    arm of chromosome 19.
  • GLUT-1 - enables basal non-insulin-stimulated
    glucose uptake into many cells
  • GLUT-2 - transports glucose into the beta-cell a
    prerequisite for glucose sensing.
  • GLUT-3 - enables non-insulin-mediated glucose
    uptake into brain neurones and placenta.
  • GLUT-4 - enables much of the peripheral action of
    insulin. It is the channel through which glucose
    is taken up into muscle and adipose tissue cells
    following stimulation of the insulin receptor .

Classification of DM
  • DM is classified on the basis of the pathogenic
    process that leads to hyperglycemia.
  • The two broad categories of DM are designated
  • Type 1 (insulin-dependent diabetes mellitus)
  • Type 2 (non-insulin-dependent diabetes mellitus)
  • Type 1 diabetes is the result of complete or
    near-total insulin deficiency.
  • Type 2 DM is a heterogeneous group of disorders
    characterized by variable degrees of insulin
    resistance, impaired insulin secretion, and
    increased glucose production.
  • Type 2 DM is preceded by a period of abnormal
    glucose homeostasis classified as impaired
    fasting glucose (IFG) or impaired glucose
    tolerance (IGT).

Secondary diabetes
  • Although secondary diabetes accounts for only
    1-2 of all new cases at presentation, it should
    not be missed because the cause can often be
  • Causes of secondary diabetes
  • Pancreatic disease
  • Cystic fibrosis
  • Chronic pancreatitis
  • Malnutrition-related pancreatic disease
  • Pancreatectomy
  • Hereditary haemochromatosis
  • Carcinoma of the pancreas

  • Endocrine disease
  • Cushing's syndrome
  • Acromegaly
  • Thyrotoxicosis
  • Phaeochromocytoma
  • Glucagonoma
  • Drug-induced disease
  • Thiazide diuretics
  • Corticosteroid therapy
  • Insulin-receptor abnormalities
  • Congenital lipodystrophy
  • Acanthosis nigricans
  • Genetic syndromes
  • Friedreich's ataxia
  • Dystrophia myotonica

Type 1 (insulin-dependent diabetes mellitus)
  • Causes
  • Type 1 diabetes belongs to a family of
    HLA-associated immune-mediated organ-specific
  • Autoantibodies directed against pancreatic islet
    constituents appear in the circulation within the
    first few years of life, prior to the clinical
    onset by many years , and also detected in cases
    of late onset auto- immune DM(LADA).
  • Genetic susceptibility Type 1 diabetes is not
    genetically predetermined, but increased
    susceptibility to the disease may be inherited

  • Inheritance
  • The identical twin of a patient with type 1
    diabetes has a 30-50 chance of developing the
    disease, indicating that additional modifying
    factors are likely involved in determining
    whether diabetes develops.
  • Children of people with type 1 diabetes have an
    increased chance of developing type 1 diabetes.
    by age 20 with a diabetic father the risk is
    (3-7),and with a diabetic mother is (2-3).
  • If one child in a family has type 1 diabetes,
    each sibling has a 6 risk of developing
    diabetes by age 20.
  • If siblings are HLA-identical (share the same
    HLA type as the affected child), the risk rises
    to about 20.

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Environmental Factors
  • Numerous environmental events have been proposed
    to trigger the autoimmune process in genetically
    susceptible individuals however, none have been
    conclusively linked to diabetes. Identification
    of an environmental trigger has been difficult
    because the event may precede the onset of DM by
    several years.
  • Putative environmental triggers include viruses
    (coxsackie and rubella most prominently), bovine
    milk proteins, and nitrosourea compounds.

Prevention of Type 1 DM
  • A number of interventions have successfully
    delayed or prevented diabetes in animal models.
  • Though results in animal models are promising,
    these interventions have not been successful in
    preventing type 1 DM in humans. The Diabetes
    Prevention Trialtype 1 concluded that
    administering insulin (IV or PO) to individuals
    at high risk for developing type 1 DM did not
    prevent type 1 DM.
  • In patients with new-onset type 1 diabetes,
    treatment with anti-CD3 monoclonal antibodies has
    recently been shown to slow the decline in
    C-peptide levels.

Type 2 (non-insulin-dependent diabetes
  • Pathogenesis
  • Hyperglycemia in type 2 diabetes likely results
    from complex genetic interactions, the expression
    of which modified by environmental factors such
    as body weight and exercise.
  • Genetic factors
  • type 2 diabetes shows a clear familial
    aggregation but does not inherited in a classic
    mendelian fashion.

  • 2- Insulin resistance
  • Type 2 diabetes is heterogeneous , both of the
    major pathogenic mechanisms i.e , impaired
    insulin secretion and impaired insulin
    action(insulin resistance or decreased insulin
    sensitivity)are operative in variable degrees in
    most patients.
  • The mechanism of insulin resistance remains
    poorly understood there is a defect in insulin
    receptor, defects in more distal (post- receptor)
    pathways play a far greater role in insulin
    resistance .
  • One important aspect of resistance is a reduced
    capacity for translocation of GLUT4 to cell
    surface in muscle cells, a separate defect in
    glycogen synthesis is also likely to be present
    and a variety of genetic abnormality in cellular
    transduction of the insulin signal.
  • Hyperglycamia per se impairs the ß cell response
    to glucose and promotes insulin resistance.

  • Abnormalities of insulin secretion manifest early
    in the course of type 2 diabetes. Normal subjects
    have a biphasic insulin response to intravenous
    glucose, but the first-phase insulin response is
    lost as hyperglycaemia develops, and insulin
    secretion in response to oral glucose is delayed
    and exaggerated.

  • Overview and prevention
  • Whether an individual develops type 2 diabetes or
    not is largely due to genetic factors.
  • When a person develops diabetes depends on
  • Clinical trials have shown that diet, exercise or
    agents such as metformin have a marked effect in
    delaying the onset of type 2 diabetes.

  • Acute presentation
  • Young people often present with a 2- to 6-week
    history and report the classic triad of symptoms
  • polyuria - due to the osmotic diuresis that
    results when blood glucose levels exceed the
    renal threshold
  • thirst - due to the resulting loss of fluid and
  • weight loss - due to fluid depletion and the
    accelerated breakdown of fat and muscle secondary
    to insulin deficiency.
  • Ketonuria is often present in young people(type
    1) and may progress to ketoacidosis if these
    early symptoms are not recognized and treated.

  • Subacute presentation
  • The clinical onset may be over several months or
    years, particularly in older patients. Thirst,
    polyuria and weight loss are typically present
    but patients may complain of such symptoms as
    easy fatigability , visual blurring (owing to
    glucose-induced changes in refraction), or
    pruritus vulvae or balanitis that is due to
    Candida infection.
  • Complications as the presenting feature
  • These include
  • staphylococcal skin infections
  • retinopathy noted during a visit to the optician
  • a polyneuropathy causing tingling and numbness in
    the feet
  • erectile dysfunction
  • arterial disease, resulting in myocardial
    infarction or peripheral gangrene.

  • Asymptomatic diabetes
  • Glycosuria or a hyperglycemia may be detected on
    routine examination (e.g. for insurance purposes)
    in individuals who have no symptoms of
  • Glycosuria is not diagnostic of diabetes but
    indicates the need for further investigations.
  • NB renal glycosuria is an inherited low renal
    threshold for glucose, transmitted either as a
    Mendelian dominant or recessive trait , with an
    incidence of about 1.
  • Physical examination at diagnosis
  • Evidence of weight loss and dehydration may be
    present, and the breath may smell of ketones.
  • Older patients may present with established
    complications, and the presence of the
    characteristic retinopathy is diagnostic of

The spectrum of diabetes a comparison of type 1
and type 2 diabetes mellitus

Type 1 (insulin dependent) Type 2 (non-insulin dependent)
Epidemiology Younger (usually lt 30 years of age) Older (usually gt 30 years of age)
  Usually lean Often overweight
  Increased in those of Northern European ancestry All racial groups. Increased in peoples of Asian, African, Polynesian and American-Indian ancestry
  Seasonal incidence  
Heredity HLA-DR3 or DR4 in gt 90 No HLA links
  30-50 concordance in identical twins 50 concordance in identical twins

Pathogenesis Autoimmune disease No immune disturbance
    Islet cell autoantibodies Insulin resistance
    Association with other autoimmune diseases  
    Immunosuppression after diagnosis delays beta-cell destruction  
Clinical Insulin deficiency Partial insulin deficiency
  May develop ketoacidosis May develop hyperosmolar state
  Always need insulin Many come to need insulin when beta-cells fail over time
Biochemical Eventual disappearance of C-peptide C-peptide persists
  • The National Diabetes Data Group and World Health
    Organization have issued diagnostic criteria for
    DM based on the following parameters (1) the
    spectrum of fasting plasma glucose (FPG) and the
    response to an oral glucose load (OGTToral
    glucose tolerance test) varies among normal
    individuals, and (2) DM is defined as the level
    of glycemia at which diabetes-specific
    complications occur rather than on deviations
    from a population-based mean. For example, the
    prevalence of retinopathy in Native Americans
    (Pima Indian population) begins to increase at a
    FPG gt 6.4 mmol/L (116 mg/dL).

Criteria for the Diagnosis of Diabetes Mellitus
  • Symptoms of diabetes 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.
  • NB The glucose tolerance test is only required
    for borderline cases and for diagnosis of
    gestational diabetes.

The glucose tolerance test - WHO criteria
Adult 75 g glucose in 300 mL water. Child 1.75
g glucose/kg bodyweight. Only a fasting and a
120-min sample are needed. Results are for
venous plasma - whole blood values are lower. NB
FPG 5.66.9 mmol/L (100125 mg/dL) is defined
as IFG

Normal Impaired glucose tolerance Diabetes mellitus
Fasting Less than 7.0 mmol/L Less than 7.0 mmol/L More than 7.0 mmol/L (126mg/dL)
2 h after glucose Less than 7.8 mmol/L(140mg/dL) Between 7.8 and 11.0 mmol/L(140 and 199 mg/dL) 11.1 mmol/L or more (200mg/dL)
  • Some investigators have advocated the hemoglobin
    A1C (A1C) as a diagnostic test for DM. Though
    there is a strong correlation between elevations
    in the plasma glucose and the A1C, the
    relationship between the FPG and the A1C in
    individuals with normal glucose tolerance or mild
    glucose intolerance is less clear, and thus the
    use of the A1C is not currently recommended to
    diagnose diabetes.
  • The diagnosis of DM has profound implications for
    an individual from both a medical and financial
    standpoint. Thus, these diagnostic criteria must
    be satisfied before assigning the diagnosis of
    DM. Abnormalities on screening tests for diabetes
    should be repeated before making a definitive
    diagnosis of DM, unless acute metabolic
    derangements or a markedly elevated plasma
    glucose are present .
  • The revised criteria also allow for the diagnosis
    of DM to be withdrawn in situations where the FPG
    reverts to normal.

  • Goals of management
  • Reduce acute and chronic complications.
  • Improve quality of life.
  • Prevent premature diabetes-related death.
  • Maintain hemoglobin A1c less than 7.
  • Clinical Standers
  • FBG 100-120 mg\dl
  • PPBG 140-160 mg\dl
  • Bedtime BG 100-140mg\dl

  • The role of patient education and community care
  • The care of diabetes is based on self-management
    by the patient, who is helped and advised by
    those with specialized knowledge , as whatever
    the technical expertise applied, the outcome
    depends on willing cooperation by the patient.
  • The best time to educate the patient is soon
    after diagnosis. Organized education programmes
    will involve all healthcare workers, including
    nurse specialists, dietitians and podiatrist.
  • Lifestyle modifications
  • Weight loss
  • Exercise
  • Dietary management

Nutritional Recommendations for Adults with
  • Fat  
  •  2035 of total caloric intake
  •   Saturated fat lt 7 of total calories   
  •  Two or more servings of fish/week provide -3
    polyunsaturated fatty acids  
  • Carbohydrate  
  •  4565 of total caloric intake (low-carbohydrate
    diets are not recommended) .
  • Amount and type of carbohydrate important
  • Sucrose-containing foods may be consumed with
    adjustments in insulin dose

  • Protein
  • 1035 of total caloric intake (high-protein
    diets are not recommended) i.e 1.0 to 1.5 g\kg
    per day, to be restricted in nephropathy 0.8 g\kg
    per day.
  • Other components
  • Fiber-containing foods may reduce postprandial
    glucose peak
  • Non-nutrient sweeteners
  • Exercise
  • Exercise has multiple positive benefits including
  • cardiovascular risk reduction,
  • reduced blood pressure,
  • maintenance of muscle mass
  • reduction in body fat
  • weight loss and lowering plasma glucose (during
    and following exercise) and increasing insulin

  • In patients with diabetes, it is recommended to
    be150 min/week (distributed over at least 3 days)
    of aerobic physical activity.
  • In patients with type 2 DM, the exercise regimen
    should also include resistance training.
  • Pharmacotherapy
  • Oral Hypoglycemic agents
  • Sulphonylureas
  • Their principal action is to promote insulin
    secretion in response to glucose
  • Minor extra panceatic role as insulin sensitizers.

Properties of the most commonly used

Drug Features
Tolbutamide Lower maximal efficacy than other sulphonylureas
  Short half-life - preferable in elderly
  Largely metabolized by liver - can use in renal impairment
Glibenclamide, glipizide and glimepiride Long biological half-lifeActive metabolitesRenal excretion - avoid in renal impairment
Gliclazide Fairly long biological half-life
  Largely metabolized by liver - can use in renal impairment
  More costly
Properties of the most commonly used
sulphonylureas (cont.)
Drug Features
Chlorpropamide Very long biological half-life
  Renal excretion - avoid in renal impairment
  1-2 develop inappropriate ADH-like syndrome
  Facial flush with alcohol
  Very inexpensive - major issue for developing countries
Drug interactions and side-effects
  • Sulphonylureas should be used with care in
    patients with liver disease, and only those
    primarily excreted by the liver should be given
    to patients with renal impairment. (Tolbutamide
  • All encourage weight gain and are therefore not
    drugs of first choice in obese patients.
  • Tolbutamide is the safest drug in the very
    elderly because of its short duration of action.
  • Hypoglycaemia is the most common and dangerous
    side-effect. Specially in long acting type eg,
  • Skin rashes and other sensitivity reactions do
    rarely occur.
  • All sulphonylureas bind to circulating albumin
    and may be displaced by other drugs, such as
    sulphonamides, that compete for their binding
    sites ,also interact with warfarin.

  • Metformin is currently the best validated primary
    treatment for type 2 diabetes.
  • Mechanism of action
  • It remains unclear but it reduces
    gluconeogenesis, thus suppressing hepatic glucose
    output, and it increases insulin sensitivity.
  • Unlike the sulphonylureas it does not induce
    hypoglycaemia in normal volunteers.
  • It is particularly helpful in the overweight
    since it does not promote weight gain.
  • It may be given in combination with
    sulphonylureas or thiazolidinediones.
  • Side-effects
  • Anorexia, epigastric discomfort and diarrhoea.
  • Lactic acidosis has occurred in patients with
    severe hepatic or renal disease, and metformin is
    contraindicated when these are present.
  • Most diabetologists withdraw the drug when serum
    creatinine exceeds 1.5 in males and 1.4 in

  • The thiazolidinediones (more conveniently known
    as the 'glitazones') reduce insulin resistance by
    interaction with peroxisome proliferator-activated
    receptor-gamma (PPAR-gamma), a nuclear receptor
    which regulates genes involved in lipid
    metabolism and insulin action.
  • One suggestion is that they act indirectly via
    the glucose-fatty acid cycle, lowering free fatty
    acid levels and thus promoting glucose
    consumption by muscle.
  • They can be used alone or in combination with
    other agents.
  • The glitazones reduce hepatic glucose production,
    an effect that is synergistic with that of
    metformin, and also enhance peripheral glucose
    uptake thus, potentiate the effect of endogenous

  • Side effects
  • Contraindicated in mild liver impairment(
    elevated serum trasaminases 2.5 times the upper
    limit ofnormal).
  • Given cautiously to patient with heart failure ,
    renal impairment.
  • Fluid retention , mild oedema and weight gain.
  • a-Glucosidase Inhibitors
  • -Glucosidase inhibitors (acarbose and miglitol)
    reduce postprandial hyperglycemia by delaying
    glucose absorption they do not affect glucose
    utilization or insulin secretion .
  • These drugs, taken just before each meal, reduce
    glucose absorption by inhibiting the enzyme that
    cleaves oligosaccharides into simple sugars in
    the intestinal lumen.

  • Side effects
  • GIT disturbance flatulence , abdominal
    distension .
  • Contraindicated in hepatic impairment.
  • Meglitinides
  • Repaglinide and nateglinide are non-sulphonylurea
    insulin secretagogues known as the meglitinides.
  • Advantages
  • Low incideace of hypoglycaemia as they are
    short-acting agents that promote insulin
    secretion in response to meals .
  • Disadvantages
  • They are more expensive than standard

Insulin treatment
  • Indications
  • Type 1 (insulin-dependent diabetes mellitus)
  • Gestational diabetes
  • Diabetic ketoacidosis, hyperosmolar diabetic coma
  • Hyperglycemia despite maximum doses of oral
  • Surgical procedures
  • Infection, acute injury, stress
  • Allergy or other serious reaction to oral agents

  • Insulin delivery methods
  • Syringes
  • Pens
  • Insulin pump
  • Inhalation

Pharmacokinetics of Insulin Preparations
Time of Action Time of Action Time of Action
Preparation Onset, h Peak, h Effective Duration, h
Short-acting, subcutaneous      
  Lispro lt0.25 0.51.5 34
  Aspart lt0.25 0.51.5 34
  Glulisine lt0.25 0.51.5 34
  Regular 0.51.0 23 46
Short-acting, inhaled      
  Inhaled regular insulin lt0.25 0.51.5 46
Preparation Onset, h Peak, h Effective Duration, h
  NPH 14 610 1016
  Detemir 14   1220
  Glargine 14   24
Insulin Combinations      
  75/2575 protamine lispro, 25 lispro lt0.25 1.5 h  Up to 1016
  70/3070 protamine aspart, 30 aspart lt0.25 1.5 h  Up to 1016
  50/5050 protamine lispro, 50 lispro lt0.25 1.5 h  Up to 1016
  70/3070 NPH, 30 regular insulin 0.51 Dual 1016
  50/5050 NPH, 50 regular insulin 0.51 Dual 1016

Insulin administration patterns
  • 1-Conventional One or two injections per day of
    intermediate acting such as zinc insulin
    (lente)or isophane(NPH) with or without the
    addition of small amount of regular insulin.
    Usual starting dose is 20 u\day.
  • Premixed preparations may be used as two thirds
    of the dose before breakfast and one third before
  • 2- Multiple S.C insulin injections intermediate
    , long acting or basal insulin single bedtime
    dose with regular insulin prior to each meal.
  • 3- Continuous S.C insulin infusion insulin pump

Guide to adjusting insulin dosage according to
blood glucose test results

Blood glucose persistently too high Blood glucose persistently too low
Before breakfast Increase evening long-acting insulin Reduce evening long-acting insulin
Before lunch Increase morning short-acting insulin Reduce morning short-acting insulin or increase mid-morning snack
Before evening meal Increase morning long-acting insulin or lunch short-acting insulin Reduce morning long-acting insulin or lunch short-acting insulin or increase mid-afternoon snack
Before bed Increase evening short-acting insulin Reduce evening short-acting insulin
Complications of insulin therapy
  • At the injection site
  • Shallow injections result in intradermal insulin
    delivery and painful, reddened lesions or even
  • Injection site abscesses occur but are extremely
  • Local allergic responses sometimes occur early in
    therapy but usually resolve spontaneously.
  • Generalized allergic responses are exceptionally
  • Fatty lumps, known as lipohypertrophy, may occur
    as the result of overuse of a single injection
    site with any type of insulin.
  • Systemic complications
  • Insulin resistance
  • Hypoglycemia
  • Weight gain ,especially if the insulin dose is
    increased inappropriately.

Monitoring the Level of Glycemic Control
  • Self-Monitoring of Blood Glucose (SMBG) The
    frequency of SMBG measurements must be
    individualized and adapted to address the goals
    of diabetes care. Individuals with type 1 DM or
    individuals with type 2 DM taking multiple
    insulin injections each day should routinely
    measure their plasma glucose three or more times
    per day to estimate and select mealtime boluses
    of short-acting insulin and to modify long-acting
    insulin doses. Most individuals with type 2 DM
    require less frequent monitoring, though the
    optimal frequency of SMBG has not been clearly
  • Assessment of Long-Term Glycemic Control
  • Glycated hemoglobin or A1C (standardized range
    4-6.5) should be measured in all individuals
    with DM during their initial evaluation and as
    part of their comprehensive diabetes care. As the
    primary predictor of long-term complications of
    DM, the A1C should mirror, to a certain extent,
    the short-term measurements of SMBG.
  • It ideally to kept lt 7.

Acute Complications of DM
  • Diabetic ketoacidosis
  • Diabetic ketoacidosis (DKA) was formerly
    considered a hallmark of type 1 DM, but it can
    occur in obese individuals with type 2 DM with
    absolute or relative insulin deficiency.
  • It is usually seen in the following
  • previously undiagnosed diabetes
  • interruption of insulin therapy
  • the stress of intercurrent illness.
  • Pathogenesis
  • DKA results from relative or absolute insulin
    deficiency combined with counter regulatory
    hormone excess (glucagon, catecholamines,
    cortisol, and growth hormone).

  • This 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
  • Rising glucose levels lead to an osmotic
    diuresis, loss of fluid and electrolytes, and
  • Plasma osmolality rises and renal perfusion
    falls. In parallel, rapid lipolysis occurs,
    leading to elevated circulating free fatty-acid
  • Accumulation of ketone bodies produces a
    metabolic acidosis. Vomiting leads to further
    loss of fluid and electrolytes.
  • ketone bodies are excreted in the urine ,and also
    appear in the breath, producing a distinctive
    smell similar to that of acetone.
  • Respiratory compensation for the acidosis leads
    to hyperventilation, 'air hunger'.
  • Progressive dehydration impairs renal excretion
    of hydrogen ions and ketones, aggravating the
  • As the pH falls below 7.0 , pH-dependent enzyme
    systems in many cells function less effectively.
  • Untreated, severe ketoacidosis is invariably

  • Clinical Features
  • Symptoms of DKA are of gradual onset , may take
    days .
  • Hyperglycemia Polyuria, nocturia, polydipsia ,
    weight loss.
  • Dehdration dry skin and tongue, hypotension,
    weak rapid pulse oliguria.
  • Acidosis(ketone bodies )Vomiting ,abdominal pain
    , acetone odour in breath and Kussmaul breathing
  • Lethargy and central nervous system depression
    may evolve into coma with severe DKA but should
    also prompt evaluation for other reasons for
    altered mental status (infection, hypoxia, etc.).
  • Cerebral edema, an extremely serious complication
    of DKA, is seen most frequently in children.
  • Signs of infection, which may precipitate DKA,
    should be sought on physical examination, even in
    the absence of fever.
  • Tissue ischemia (heart, brain) can also be a
    precipitating factor.

Management 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 lt 7.00
    or unconscious.
  • Assess
  • Serum electrolytes (K, Na, Mg2, Cl-,
    bicarbonate, phosphate)
  • Acid-base statuspH, HCO3-, PCO2,
  • Renal function (creatinine, urine output)
  • Replace fluids 23 L of 0.9 saline over first
    13 h (1015 mL/kg per hour) subsequently, 0.45
    saline at 150300 mL/h change to 5 glucose and
    0.45 saline at 100200 mL/h when plasma glucose
    reaches 250 mg/dL (14 mmol/L).
  • 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 24 h. If initial
    serum potassium is lt 3.3 meq/L, do not administer
    insulin until the potassium is corrected to gt 3.3
  • Assess patient What precipitated the episode
    (noncompliance, infection, trauma, infarction)?
    Initiate appropriate workup for precipitating
    event (cultures, CXR, ECG).

  • Measure capillary glucose every 12 h measure
    electrolytes (especially K, bicarbonate,
    phosphate) and anion gap every 4 h for first 24
  • Monitor blood pressure, pulse, respirations,
    mental status, fluid intake and output every 14
  • Replace K 10 meq/h when plasma K lt 5.5 meq/L,
    ECG normal, urine flow and normal creatinine
    documented administer 4080 meq/h when plasma K
    lt 3.5 meq/L or if bicarbonate is given.
  • Continue above until patient is stable, glucose
    goal is 150250 mg/dL, and acidosis is resolved.
    Insulin infusion may be decreased to 0.050.1
    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

Hyperglycemic Hyperosmolar Non-ketotic
  • It is a metabolic emergency characteristic of
    old uncontrolled type 2 diabetes.
  • Common precipitating factors include
  • Consumption of glucose-rich fluids .
  • Concurrent medication such as thiazide diuretics
    or steroids.
  • Intercurrent illness.
  • N.B Non-ketotic coma and ketoacidosis represent
    two ends of a spectrum rather than two distinct

  • 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 counter regulatory hormones and free
    fatty acids, and also may be because that the
    liver is less capable of ketone body synthesis or
    that the insulin/glucagon ratio does not favor

Clinical Features
  • dehydration and stupor or coma Impairment of
    consciousness is directly related to the degree
    of hyperosmolality.
  • Evidence of underlying illness such as pneumonia
    or pyelonephritis may be present.
  • The hyperosmolar state may predispose to stroke,
    myocardial infarction or arterial insufficiency
    in the lower limbs.
  • Laboratory Abnormalities and Diagnosis
  • Sever hyperglycemia plasma glucose may be gt55.5
    mmol/L (1000 mg/dL).
  • Hyperosmolality (gt350 mosmol/L).
  • Prerenal azotemia.
  • In contrast to DKA, acidosis and ketonemia are
    absent or mild,but small anion gap metabolic
    acidosis may be present secondary to increased
    lactic acid.
  • Moderate ketonuria, if present, is secondary to

  • N.B
  • The normal range of osmolality is 285-300
    mOsm/kg. It can be measured directly, or can be
    calculated approximately from the formula
    Osmolality 2(Na K) glucose urea
    (all in mmol/L).
  • The normal anion gap is less than 17. It is
    calculated as (Na K) - (Cl- HCO3-).
  • Treatment
  • Fluid replacement should initially stabilize the
    hemodynamic status of the patient (13 L of 0.9
    normal saline over the first 23 h). 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.
  • If the serum sodium gt 150 meq/L, 0.45 saline
    should be used. After hemodynamic stability is
    achieved, the IV fluid administration is directed
    at reversing the free water deficit using
    hypotonic fluids (0.45 saline initially then 5
    dextrose in water, D5W).

  • The calculated free water deficit (which averages
    910 L) should be reversed over the next 12 days
    (infusion rates of 200300 mL/h of hypotonic
    solution)guided by CV line monitoring of the
    volume status.
  • Insulin and K supplement are like DKA.
  • Treatment of the underlying illness.
  • Prognosis
  • The reported mortality ranges as high as 20-30,
    mainly because of the advanced age of the
    patients and the frequency of intercurrent

Lactic acidosis
  • Lactic acidosis may occur in diabetic patients on
    biguanide therapy, if the therapeutic dose is
    exceeded or the drug is not withheld in patients
    with advanced hepatic or renal dysfunction.
  • Patients present in severe metabolic acidosis
    with a large anion gap (normally less than 17
    mmol/L), usually without significant
    hyperglycaemia or ketosis.
  • Treatment
  • Rehydration and infusion of isotonic 1.26
  • Prognosis
  • The mortality is in excess of 50.

  • It occurs more common in type 1 DM especially
    those on intensive insulin therapy, but it is
    rare with the recent insulin analogues that have
    no high beaks as old insulin formula.
  • Pathogenesis
  • In normal subjects , fasting results in release
    of adrenaline and glucagon to stimulate
    glycogenolysis and gluconeogenesis .This hormone
    release is blunted in type 1 DM .
  • NB
  • If hypoglycemia occurs in type 2 DM on oral
    hypoglycemic agents ,it is more prolonged ,more
    sever ,so the pt should be hospitalized and
    monitored for at least 24 h after resolution of
    the attack.

  • Predisposing factors
  • Missed or small meal
  • Over dose of insulin
  • Unexpected increased activity.
  • Clinical Features
  • The most common symptoms and signs of
    hypoglycaemia are neurological as the brain
    consumes about 50 of the total glucose produced
    by the liver these include cold sweating
    ,shaking, tachycardia, dilated pupils and
    tremors.(release of adrenaline )
  • If the condition is prolonged pt will develop
    cognitive impairment, dizziness, hunger,
    convulsions, coma without lateralizing signs and
    bilateral extensor planter response ,and
    irreversible brain damage death. (decrease
    glucose supply to the brain which is the only

  • If the pt is conscious a sugary fluid is given
    and a meal is taken after 15 minutes
  • If the pt is unconscious IV glucose ( 25-50 ml
  • Glucagon 1mg IM
  • Searching for and correcting the predisposing

Chronic Complications of DM
  • The chronic complications of DM affect many organ
    systems and are responsible for the majority of
    morbidity and mortality associated with the
    disease these include
  • Microvascular complications
  • Retinopathy,(non proliferative/proliferative),
    macular edema
  • Neuropathy sensory and motor(mono- and
    polyneuropathy), autonomic
  • Nephropathy
  • Macrovascular complications
  •  Coronary artery disease
  •   Peripheral arterial disease
  •   Cerebrovascular disease

  • Other complications
  • Gastrointestinal (gastroparesis, diarrhea)
  •  Genitourinary (uropathy/sexual dysfunction)  
  •  Dermatologic infectious  
  •  Cataracts
  •   Glaucoma   
  • Periodontal disease

Mechanisms of Complications
  • Although chronic hyperglycemia is an important
    etiologic factor leading to complications of DM,
    the mechanism(s) by which it leads to such
    diverse cellular and organ dysfunction is
  • Four prominent theories, have been proposed to
    explain how hyperglycemia might lead to the
    chronic complications of DM.
  • One theory
  • the increased intracellular glucose leads to the
    formation of advanced glycosylation end products
    (AGEs) via the nonenzymatic glycosylation of
    intra- and extracellular proteins. AGEs have been
    shown to cross-link proteins (e.g., collagen,
    extracellular matrix proteins), accelerate
    atherosclerosis, promote glomerular dysfunction,
    reduce nitric oxide synthesis, induce endothelial
    dysfunction, and alter extracellular matrix
    composition and structure.
  • The serum level of AGEs correlates with the
    level of glycemia, and these products accumulate
    as glomerular filtration rate declines.

  • A second theory
  • It is based on the observation that hyperglycemia
    increases glucose metabolism via the sorbitol
    pathway by the enzyme aldose reductase. Increased
    sorbitol concentration increases cellular
    osmolality, generates reactive oxygen species,
    and likely leads to other types of cellular
    dysfunction. However, testing of this theory in
    humans, using aldose reductase inhibitors, has
    not demonstrated significant beneficial effects
    on clinical endpoints of retinopathy, neuropathy,
    or nephropathy.
  • A third hypothesis proposes that hyperglycemia
    increases the formation of diacylglycerol leading
    to activation of protein kinase C (PKC). Among
    other actions, PKC alters the cellular membrane
    ,and plasma lipoproteins rendering them more
    atherogenic. endothelial cells and neurons.
    Inhibitors of PKC are being studied in clinical

  • A fourth theory proposes that hyperglycemia
    increases the flux through the hexosamine
    pathway. The hexosamine pathway may alter
    function by glycosylation of proteins such as
    endothelial nitric oxide synthase or by changes
    in gene expression of transforming growth factor
    (TGF-) or plasminogen activator inhibitor-1
  • Growth factors as appear to play an important
    role in DM-related complications, and their
    production is increased by most of these proposed
    pathways. Vascular endothelial growth factor A
    (VEGF-A) is increased locally in diabetic
    proliferative retinopathy. TGF- is increased in
    diabetic nephropathy and stimulates basement
    membrane production of collagen and fibronectin
    by mesangial cells. Other growth factors, such as
    platelet-derived growth factor, epidermal growth
    factor, insulin-like growth factor I, growth
    hormone, basic fibroblast growth factor, and even
    insulin, have been suggested to play a role in
    DM-related complications.

  • A possible unifying mechanism is that
    hyperglycemia leads to increased production of
    reactive oxygen species or superoxide in the
    mitochondria these compounds may activate all
    four of the pathways described above. Although
    hyperglycemia serves as the initial trigger for
    complications of diabetes, it is still unknown
    whether the same pathophysiologic processes are
    operative in all complications or whether some
    pathways predominate in certain organs.

Ophthalmologic Complications of Diabetes Mellitus
  • DM is the leading cause of blindness between the
    ages of 20 and 74 in the United
    States,individuals with DM are 25 times more
    likely to become legally blind than individuals
    without DM.
  • Blindness is primarily the result of progressive
    diabetic retinopathy and clinically significant
    macular edema.
  • Diabetic retinopathy is classified into two
  • Nonproliferative diabetic retinopathy usually
    appears late in the first decade or early in the
    second decade of the disease and is marked by
    retinal vascular microaneurysms, blot
    hemorrhages, and cotton wool spots. Alterations
    in retinal blood flow, increased retinal vascular
    permeability and abnormal retinal
    microvasculature, all of which lead to retinal
  • Proliferative diabetic retinopathyThe
    appearance of neovascularization in response to
    retinal hypoxia is the hallmark of proliferative
    diabetic retinopathy

  • These newly formed vessels appear near the optic
    nerve and/or macula and rupture easily, leading
    to vitreous hemorrhage, fibrosis, and ultimately
    retinal detachment.
  • Duration of DM and degree of glycemic control are
    the best predictors of the development of
    retinopathy hypertension is also a risk factor.
    Non proliferative retinopathy is found in almost
    all individuals who have had DM for gt20 years
    (25 incidence with 5 years, and 80 incidence
    with 15 years of type 1 DM).
  • Treatment
  • Early detection and treatment Annual
    ophthalmologic examinations should begin within
    5years in type1 and at the time of disease
    detection in type 2.
  • Optimization of glycemic control delays and slows
    progression of non-proliferative retinopathy with
    only little evidence in proliferative retinopathy
  • Aggressive control of hypertension.
  • Retinal LASER photocoagulation if progressive
    retinopathy threatens vision.
  • Surgical treatmentVitrectomy in vitreous
    hemorrhage or to cut extensive fibrous bands
    causing retinal detachments.

Diabetic nephropathy
  • It is the leading cause of ESRD worldwide and a
    leading cause of DM-related morbidity and
  • It is usually manifests 15-25 years after
    diagnosis and affects 25-35 of patients
    diagnosed under the age of 30 years.
  • Pathophysiology
  • The earliest functional abnormality in the
    diabetic kidney is renal hypertrophy associated
    with a raised glomerular filtration rate. This is
    related to poor glycaemic control.
  • As the kidney becomes damaged by diabetes, the
    afferent arteriole becomes vasodilated to a
    greater extent than the efferent glomerular
    arteriole. This increases the intraglomerular
    filtration pressure, leads to further damaging
    the glomerular capillaries and increased shearing
    forces locally which are thought to contribute to
    mesangial cell hypertrophy and increased
    secretion of extracellular mesangial matrix
    material. This process eventually leads to
    glomerular sclerosis.

  • Albuminuria At first 'microalbuminuria' -
    amounts of urinary albumin so small ,may be
    tested for by radioimmunoassay or by using
    special dipsticks.
  • It is a predictive marker of progression to
    nephropathy in type 1 diabetes, and of increased
    cardiovascular risk in type 2 diabetes.
  • progression to overt proteinuria (gt300 mg/d),
    only 50 of individuals progress to
    macroalbuminuria over the next 10 years.
  • Once macroalbuminuria is present, there is a
    steady decline in GFR, and 50 of individuals
    reach ESRD in 710 years.
  • Once macroalbuminuria develops, blood pressure
    rises slightly and the pathologic changes are
    likely irreversible.
  • NB Some individuals with type 1 or type 2 DM
    have a decline in GFR in the absence of micro- or
    macroalbuminuria and this is the basis for
    assessing the GFR on an annual basis using serum

  • Ischaemic lesions
  • Arteriolar lesions, with hypertrophy and
    hyalinization of the vessels, can occur in
    patients with diabetes. The appearances are
    similar to those of hypertensive disease and lead
    to ischaemic damage to the kidneys.
  • Diagnosis
  • 1-Urine albumin assay
  • As the onset of diabetic nephropathy is often
    silent screening of younger patients for
    microalbuminuria has to be done routinely, since
    there is evidence that meticulous glycaemic
    control or early antihypertensive treatment at
    this stage may delay the onset of frank
  • Once proteinuria is present, other possible
    causes for this should be considered ,also assay
    should be done in absence of urinary tract
    infection,DKA, and vigorous exercise.

  • 2- Serum urea , Creatinine , Creatinine
  • 3-Abdominal ultrasound to exclude obstractive
  • 4- Fundus examination in almost all cases of
    diabetic nephropathy ,diabetic retinopathy is
  • Management
  • Improved glycemic control reduces the rate at
    which microalbuminuria appears and progresses in
    type 1 and type 2 DM. However, once
    macroalbuminuria exists, it is unclear whether
    improved glycemic control will slow progression
    of renal disease. During the phase of declining
    renal function, insulin requirements may fall as
    the kidney is a site of insulin degradation.
    Furthermore, many glucose-lowering medications
    (sulfonylureas and metformin) are contraindicated
    in advanced renal insufficiency.
  • Aggressive treatment of blood pressure with a
    target below 130/80 mmHg has been shown to slow
    the rate of deterioration of renal failure
    considerably. Angiotensin-converting enzyme
    inhibitors or an angiotensin receptor II
    antagonist are the drugs of choice.

  • These drugs should also be used in normotensive
    patients with persistent microalbuminuria as
    reduction in albuminuria occurs with this
  • Associated diabetic retinopathy tends to progress
    rapidly, and frequent ophthalmic supervision is
  • Management of ESRD is made more difficult by the
    fact that patients often have other complications
    of diabetes such as blindness, autonomic
    neuropathy or peripheral vascular disease.
    Vascular shunts tend to calcify rapidly and hence
    chronic ambulatory peritoneal dialysis may be
    preferable to haemodialysis.
  • The failure rate of renal transplants is somewhat
    higher than in non-diabetic patients. A segmental
    pancreatic graft is sometimes performed at the
    same time as a renal graft .

Diabetic neuropathy
  • It 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,
    hypertension ,and elevated triglycerides.
  • It is recommended to screen for distal symmetric
    neuropathy beginning with the initial diagnosis
    of diabetes and screen for autonomic neuropathy 5
    years after diagnosis of type 1 DM and at the
    time of diagnosis of type 2 DM.
  • All individuals with diabetes should then be
    screened annually for both forms of neuropathy.

  • Pathophysiology
  • The earliest functional change in diabetic nerves
    is delayed nerve conduction velocity the
    earliest histological change is segmental
    demyelination, caused by damage to Schwann cells.
  • In the early stages axons are preserved,
    implying prospects of recovery, but at a later
    stage irreversible axonal degeneration develops.
  • The following varieties of neuropathy occur
  • symmetrical mainly sensory polyneuropathy
  • acute painful neuropathy
  • mononeuropathy and mononeuritis multiplex
  • (a) cranial nerve lesions
  • (b) isolated peripheral nerve lesions
  • diabetic amyotrophy
  • autonomic neuropathy.

  • Symmetrical mainly sensory polyneuropathy
  • It is the most common form of diabetic
  • It most frequently presents with distal sensory
    loss (deep before superficial), but up to 50 of
    patients do not have symptoms of neuropathy.
  • Hyperesthesia and paresthesia also may occur.
  • As neuropathy progresses any combination of these
    symptoms may develop including a sensation of
    numbness, tingling, sharpness, or burning that
    begins in the feet and spreads proximally.
  • Involvement of the hands is much less common and
    results in a 'stocking and glove' sensory loss.
  • Complications include unrecognized trauma,
    beginning as blistering due to an ill-fitting
    shoe, and leading to ulceration.

  • Diabetic polyradiculopathy is a syndrome
    characterized by severe disabling pain in the
    distribution of one or more nerve roots.
  • It may be accompanied by motor weakness.
  • 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, diabetic polyradiculopathies are
    usually self-limited and resolve over 612
  • 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
  • A vascular etiology has been suggested, but the
    pathogenesis is unknown.
  • Involvement of the third cranial nerve is most
    common and is heralded by diplopia. 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.

  • Acute painful neuropathy A diffuse, painful
    neuropathy is less common. The patient describes
    burning or crawling pains in the feet, shins and
    anterior thighs. These symptoms are typically
    worse at night, and pressure from bedclothes may
    be intolerable.
  • It may present at diagnosis or develop after
    sudden improvement in glycaemic control (e.g.
    when insulin is started). It usually remits
    spontaneously after 3-12 months if good control
    is maintained.
  • A more chronic form, developing later in the
    course of the disease, is sometimes resistant to
    almost all forms of therapy.
  • Neurological assessment is difficult because of
    the hyperaesthesia experienced by the patient.

  • Autonomic neuropathy
  • Asymptomatic autonomic disturbances can be
    demonstrated on laboratory testing in many
    patients, but symptomatic autonomic neuropathy is
  • It affects both the sympathetic and
    parasympathetic nervous systems.
  • The cardiovascular system
  • Vagal neuropathy results in tachycardia at rest
    ,loss of sinus arrhythmia,loss of cardiovascular
    reflexes such as the Valsalva maneuver are
    impaired , postural hypotension occurs owing to
    loss of sympathetic tone to peripheral arterioles
    , and warm foot with a bounding pulse as a result
    of peripheral vasodilatation.
  • Gastrointestinal tract Vagal damage can lead to
  • gastroparesis, often asymptomatic, but sometimes
    leading to intractable vomiting.
  • Autonomic diarrhoea often occurs at night
    accompanied by urgency and incontinence.
  • Diarrhoea and steatorrhoea may occur owing to
    small bowel bacterial overgrowth treatment is
    with antibiotics such as tetracycline.
  • Constipation is the most commen symptom, but
    diarrhoea is the most distressing.
  • Urinary bladder involvement Loss of tone,
    incomplete emptying, and stasis (predisposing to
    infection) resulting in an atonic, painless,
    distended bladder.

  • Male erectile dysfunction
  • Erectile dysfunction in diabetes has many causes
    including anxiety, depression, alcohol excess,
    drugs, primary or secondary gonadal failure,
    hypothyroidism, and inadequate vascular supply
    owing to atheroma in pudendal arteries.
  • The history and examination should focus on these
    possible causes. Blood is taken for LH, FSH,
    testosterone, prolactin and thyroid function.
  • Skin and sweat glands
  • Distal anhydrosis ,gustatory sweating
    ,compensatory truncal and facial sweating

  • Treatment
  • Treatment of diabetic neuropathy is less than
  • Improved glycemic control should be aggressively
    done and will improve nerve conduction velocity,
    but symptoms of diabetic neuropathy may not
    necessarily improve.
  • Risk factors for neuropathy such as hypertension
    and hypertriglyceridemia should be treated.
  • Chronic, painful diabetic neuropathy is difficult
    to treat but may respond to antidepressants or
    anticonvulsants .
  • Aldose reductase inhibitors do not offer
    significant symptomatic relief.
  • Since the pain of acute diabetic neuropathy may
    resolve over time, medications may be
    discontinued as progressive neuronal damage from
    DM occurs.
  • For gastroparisis agents with some efficacy
    include dopamine agonists metoclopramide, and
    domperidone before each meal.
  • Erythromycin interacts with the motilin receptor
    and may promote gastric emptying. Treatment of
    bacterial overgrowth with antibiotics is
    sometimes useful .
  • Diabetic diarrhea in the absence of bacterial
    overgrowth is treated symptomatically.

  • Diabetic cystopathy should be treated with timed
    voiding or self-catheterization, possibly with
    the addition of bethanechol.
  • Drugs that inhibit type 5 phosphodiesterase are
    effective for erectile dysfunction, but their
    efficacy in individuals with DM is slightly lower
    than in the nondiabetic population .
  • Sexual dysfunction in women may be improved with
    use of vaginal lubricants, treatment of vaginal
    infections, and systemic or local estrogen
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