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DIABETES & GLYCEMIC
DISORDERS
 THREE MAIN CATEGORIES OF DM
1. TYPE 1 (previously called insulin dependent DM or juvenile
onset DM).
2. TYPE 2 (Previously called non insulin dependent DM or
adult onset DM)
3. Gestational diabetes (diabetes diagnosed in pregnancy)
 TYPE 1 DM:
a) Accounts for approximately 5-10% of patients and is generally due
to autoimmune destruction of the pancreatic beta cells, leading to
absolute insulin deficiency.
b) Although typically diagnosed in patients before age 30, it can
present at any age due to variability in the rate of beta cell
destruction.
 MAJOR CHARACETRISTICS OF TYPE 2 DM.
1. Majority of patients have type 2 DM,which is associated with insulin
resistance and relative insulin deficiency
2. Most patients are obese(predominantly abdominal accumulation).
3. Diagnosed in adult hood, and patients are not prone to develop
ketoacidosis except in association with the stress from another illness.
 General features of type 1 and type 2 DM.
TYPE 1 DM TYPE 2 DM
USUALLY PRESENT AT YOUNGER AGE TYPICALLY PRESENTS AGE >40
NORMAL WEIGHT OR THIN OBESE
USUALLY NO FAMILY HISTORY STRONG FAMILY HISTORY
AUTOIMMUNE MARKERS MAY BE
POSITIVE
NOT AUTOIMMUNE IN NATURE
INSULIN SENSITIVE INSULIN RESISTANT
REQUIRES INSULIN FOR TREATMENT OFTEN MANAGED WITH DIET OR ORAL
AGENTS
USUALLY EVENTUALLY REQUIRE
INSULIN
 GESTATIONAL DM
1. Diagnosed during pregnancy
2. Occurs in approximately 4% of pregnant women.
3. Presents in 2nd or 3rd trimester when insulin resistance normally occurs.
4. Its associated with increased fetal morbidity and mortality.
5. Glucose tolerance usually returns to normal after delivery, but 30-40%
of women with gestational DM develop type 2 DM within 10 years.
 OTHER SPECIFIC TYPES OF DM.
1. Include genetic defects in beta cell function, also known as maturity onset DM
of young
2. Genetic defects in insulin action(mutation in the insulin receptor)
3. Disease of exocrine pancreas (eg: hemochromatosis,neoplasm,cystic fibrosis)
4. Endocrinopathies ( eg: Cushing's
syndrome,acromegaly,somatostatinoma,glucagonoma)
5. Drug induced DM (eg: pentamidine,glucocorticoids,alpha interferon)
 Two sets of criteria in routine clinical use for the diagnosis of DM.
1. Symptoms of diabetes plus causal plasma glucose ≥ 200 mg/dl
2. Fasting Plasma glucose ≥ 126 mg/dl. Fasting is defined as no caloric
intake for at least 8 hours.
 What caveat applies to both sets of criteria?
In the absence of unequivocal hyperglycemia with acute metabolic
decompensation, these criteria should be confirmed by repeat testing on a
different day.
 Oral glucose tolerance test (OGTT)
1. The OGTT is a specialized test for the diagnosis of DM.
2. The test should be performed as described by the World Health
Organization, using a glucose load containing the equivalent of 75 gm
of anhydrous glucose dissolved in water.
3. A positive test is defined as 2-hour PG ≥ 200 mg/dL (11.1 mmol/L).
4. The OGTT is an accepted method for diagnosing DM; it is just not
used routinely because it is more cumbersome than the other criteria
PRE-DIABETES
 Pre-diabetes refers to an intermediate group of people who have
glucose values too high to be considered normal but do not fit the
criteria for the diagnosis of DM. They are at high risk of
developing DM. This group includes patients with impaired
glucose tolerance (IGT) and impaired fasting glucose (IFG).
IGT AND IFG
 IGT is defined as a 2-hour postload glucose of 140-199 mg/dL
(7.8-11.1 mmol/L), using the OGTT.
 IFG is defined as fasting PG of 100-125 mg/dL (5.6-6.9
mmol/L).
 IGT and IFG are not truly disease entities but are associated
with the metabolic syndrome and a high risk of developing DM and
cardiovascular disease
CHARACTERISTICS OF THE
METABOLIC SYNDROME.
 The metabolic syndrome refers to a constellation of signs and symptoms that are associated with
an increased risk of cardiovascular disease and include: Pre-diabetes or diabetes (hyperinsulinemia)
 Abdominal (central) obesity
 Hypertension
 Atherosclerosis
 Polycystic ovarian syndrome
 Atherogenic dyslipidemia (elevated triglycerides, apolipoprotein B, small dense LDL and low
HDL)
 Altered coagulant state (impaired fibrinolysis, increased plasminogen activator inhibitor-1)
 Proinflammatory state (elevated C-reactive peptide)
THREE KEY POINTS: DIAGNOSTIC FEATURES
OF METABOLIC SYNDROME (THREE OR MORE
OF THE FOLLOWING)
1.Abdominal obesity (waist circumference: men > 40
inches (102 cm), women > 35 inches (88 cm)
2.Hypertriglyceridemia (≥ 150 mg/dL)
3.Low HDL cholesterol (men < 40 mg/dL, women < 50
mg/dL)
4.Hypertension (≥ 130/85 mmHg)
5.Fasting hyperglycemia (≥ 110 mg/dL)
PATHOPHY SIOLOGY OF D I A B E T I C
KETOA C ID OSIS ( D KA ) .
 The pathogenesis of DKA involves an increase in counter-regulatory hormones
(catecholamines, cortisol, glucagon, and growth hormone), accompanied by insulin
deficiency.
 All of these hormonal factors contribute to increased hepatic and renal glucose
production and decreased peripheral glucose utilization.
 These hormonal changes also serve to enhance lipolysis and ketogenesis as well as
glycogenolysis and gluconeogenesis and serve to worsen hyperglycemia and acidosis.
 Lipolysis leads to increased free fatty acid synthesis for ultimate conversion by the liver
to ketones. This state is associated with increased production and decreased utilization of
glucose and ketones. Glucosuria leads to osmotic diuresis and dehydration that is associated
with reduced renal function and worsening acidosis.
CLINICAL FEATURES OF DKA
 Clinical features vary with the severity of DKA: polydipsia,
polyphagia, polyuria, severe dehydration, altered mental status
(ranges from normal to coma), gastrointestinal distress (nausea,
vomiting, abdominal pain), weight loss, and weakness
PHYSICAL EXAM FINDINGS
ASSOCIATED WITH DKA
 Physical exam findings also vary with the severity of DKA:
dehydration, poor skin turgor, Kussmaul breathing (deep, sighing
respiration) mental status changes (wide range), hypotension,
tachycardia, musty (fruity) breath, hyporeflexia, and hypothermia.
Untreated DKA can progress to coma, shock, and death.
LAB DATA ASSOCIATED WITH
D KA .
Lab data, which vary with the severity of DKA, include
PG > 250 mg/dL, arterial pH < 7.3, serum bicarbonate <
18 mEq/L, positive serum and urine ketones, and elevated
anion gap (> 10-12). Although the above lab results are
diagnostic for DKA, one may see other abnormalities,
including: elevated blood urea nitrogen and creatinine
with dehydration, leukocytosis, low serum sodium, and
elevated serum potassium due to extracellular shifting
caused by insulin deficiency
HYPERGLYCEMIC
HYPEROSMOLAR NON KETOTIC
SYNDROME (HHNS)?
 Patients with HHNS present with severe hyperglycemia, profound
dehydration, and some degree of alteration in mental status (50%).
Typically patients have type 2 DM and mild renal impairment. The
plasma glucose is frequently very elevated (> 600 mg/dL). Ketosis is
usually only very mild or absent. Patients typically have severe
dehydration, and plasma hyperosmolarity (> 340 mOsm/L) is one
hallmark of this condition.
HEMOGLOBIN A1C?
 Hemoglobin A1c (glycohemoglobin) is glycosylated hemoglobin and is used
as a measure of average serum glucose concentrations over the prior 2-3 months
 Hemoglobin A1c is an overall indicator of glycemic control. It should be
measured biannually in patients who meet treatment goals (typically A1c < 7%) or
quarterly in patients whose therapy is actively changing. Although an ideal goal
for A1c is < 7%, this goal must be individualized. Less intensive goals may be
indicated in patients with frequent hypoglycemia, and more intensive goals may
be desired in some patients to further reduce diabetes complications.
CHRONIC COMPLICATIONS OF
DM.
 Microvascular
 Neuropathy (painful paresthesia's, autonomic neuropathy)
 Retinopathy (non proliferative and proliferative retinopathy,
blindness)
 Nephropathy (spectrum of disease from microalbuminuria to end-
stage renal disease
 Macrovascular
 (cardiovascular and peripheral vascular disease)
 Nonhealing ulcers, amputations
 Hypertension
 Dyslipidemia
THANK YOU

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Diabetes &amp; glycemic disorders

  • 2.  THREE MAIN CATEGORIES OF DM 1. TYPE 1 (previously called insulin dependent DM or juvenile onset DM). 2. TYPE 2 (Previously called non insulin dependent DM or adult onset DM) 3. Gestational diabetes (diabetes diagnosed in pregnancy)
  • 3.  TYPE 1 DM: a) Accounts for approximately 5-10% of patients and is generally due to autoimmune destruction of the pancreatic beta cells, leading to absolute insulin deficiency. b) Although typically diagnosed in patients before age 30, it can present at any age due to variability in the rate of beta cell destruction.
  • 4.  MAJOR CHARACETRISTICS OF TYPE 2 DM. 1. Majority of patients have type 2 DM,which is associated with insulin resistance and relative insulin deficiency 2. Most patients are obese(predominantly abdominal accumulation). 3. Diagnosed in adult hood, and patients are not prone to develop ketoacidosis except in association with the stress from another illness.
  • 5.  General features of type 1 and type 2 DM. TYPE 1 DM TYPE 2 DM USUALLY PRESENT AT YOUNGER AGE TYPICALLY PRESENTS AGE >40 NORMAL WEIGHT OR THIN OBESE USUALLY NO FAMILY HISTORY STRONG FAMILY HISTORY AUTOIMMUNE MARKERS MAY BE POSITIVE NOT AUTOIMMUNE IN NATURE INSULIN SENSITIVE INSULIN RESISTANT REQUIRES INSULIN FOR TREATMENT OFTEN MANAGED WITH DIET OR ORAL AGENTS USUALLY EVENTUALLY REQUIRE INSULIN
  • 6.  GESTATIONAL DM 1. Diagnosed during pregnancy 2. Occurs in approximately 4% of pregnant women. 3. Presents in 2nd or 3rd trimester when insulin resistance normally occurs. 4. Its associated with increased fetal morbidity and mortality. 5. Glucose tolerance usually returns to normal after delivery, but 30-40% of women with gestational DM develop type 2 DM within 10 years.
  • 7.  OTHER SPECIFIC TYPES OF DM. 1. Include genetic defects in beta cell function, also known as maturity onset DM of young 2. Genetic defects in insulin action(mutation in the insulin receptor) 3. Disease of exocrine pancreas (eg: hemochromatosis,neoplasm,cystic fibrosis) 4. Endocrinopathies ( eg: Cushing's syndrome,acromegaly,somatostatinoma,glucagonoma) 5. Drug induced DM (eg: pentamidine,glucocorticoids,alpha interferon)
  • 8.  Two sets of criteria in routine clinical use for the diagnosis of DM. 1. Symptoms of diabetes plus causal plasma glucose ≥ 200 mg/dl 2. Fasting Plasma glucose ≥ 126 mg/dl. Fasting is defined as no caloric intake for at least 8 hours.  What caveat applies to both sets of criteria? In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeat testing on a different day.
  • 9.  Oral glucose tolerance test (OGTT) 1. The OGTT is a specialized test for the diagnosis of DM. 2. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 gm of anhydrous glucose dissolved in water. 3. A positive test is defined as 2-hour PG ≥ 200 mg/dL (11.1 mmol/L). 4. The OGTT is an accepted method for diagnosing DM; it is just not used routinely because it is more cumbersome than the other criteria
  • 10. PRE-DIABETES  Pre-diabetes refers to an intermediate group of people who have glucose values too high to be considered normal but do not fit the criteria for the diagnosis of DM. They are at high risk of developing DM. This group includes patients with impaired glucose tolerance (IGT) and impaired fasting glucose (IFG).
  • 11. IGT AND IFG  IGT is defined as a 2-hour postload glucose of 140-199 mg/dL (7.8-11.1 mmol/L), using the OGTT.  IFG is defined as fasting PG of 100-125 mg/dL (5.6-6.9 mmol/L).  IGT and IFG are not truly disease entities but are associated with the metabolic syndrome and a high risk of developing DM and cardiovascular disease
  • 12. CHARACTERISTICS OF THE METABOLIC SYNDROME.  The metabolic syndrome refers to a constellation of signs and symptoms that are associated with an increased risk of cardiovascular disease and include: Pre-diabetes or diabetes (hyperinsulinemia)  Abdominal (central) obesity  Hypertension  Atherosclerosis  Polycystic ovarian syndrome  Atherogenic dyslipidemia (elevated triglycerides, apolipoprotein B, small dense LDL and low HDL)  Altered coagulant state (impaired fibrinolysis, increased plasminogen activator inhibitor-1)  Proinflammatory state (elevated C-reactive peptide)
  • 13. THREE KEY POINTS: DIAGNOSTIC FEATURES OF METABOLIC SYNDROME (THREE OR MORE OF THE FOLLOWING) 1.Abdominal obesity (waist circumference: men > 40 inches (102 cm), women > 35 inches (88 cm) 2.Hypertriglyceridemia (≥ 150 mg/dL) 3.Low HDL cholesterol (men < 40 mg/dL, women < 50 mg/dL) 4.Hypertension (≥ 130/85 mmHg) 5.Fasting hyperglycemia (≥ 110 mg/dL)
  • 14. PATHOPHY SIOLOGY OF D I A B E T I C KETOA C ID OSIS ( D KA ) .  The pathogenesis of DKA involves an increase in counter-regulatory hormones (catecholamines, cortisol, glucagon, and growth hormone), accompanied by insulin deficiency.  All of these hormonal factors contribute to increased hepatic and renal glucose production and decreased peripheral glucose utilization.  These hormonal changes also serve to enhance lipolysis and ketogenesis as well as glycogenolysis and gluconeogenesis and serve to worsen hyperglycemia and acidosis.  Lipolysis leads to increased free fatty acid synthesis for ultimate conversion by the liver to ketones. This state is associated with increased production and decreased utilization of glucose and ketones. Glucosuria leads to osmotic diuresis and dehydration that is associated with reduced renal function and worsening acidosis.
  • 15. CLINICAL FEATURES OF DKA  Clinical features vary with the severity of DKA: polydipsia, polyphagia, polyuria, severe dehydration, altered mental status (ranges from normal to coma), gastrointestinal distress (nausea, vomiting, abdominal pain), weight loss, and weakness
  • 16. PHYSICAL EXAM FINDINGS ASSOCIATED WITH DKA  Physical exam findings also vary with the severity of DKA: dehydration, poor skin turgor, Kussmaul breathing (deep, sighing respiration) mental status changes (wide range), hypotension, tachycardia, musty (fruity) breath, hyporeflexia, and hypothermia. Untreated DKA can progress to coma, shock, and death.
  • 17. LAB DATA ASSOCIATED WITH D KA . Lab data, which vary with the severity of DKA, include PG > 250 mg/dL, arterial pH < 7.3, serum bicarbonate < 18 mEq/L, positive serum and urine ketones, and elevated anion gap (> 10-12). Although the above lab results are diagnostic for DKA, one may see other abnormalities, including: elevated blood urea nitrogen and creatinine with dehydration, leukocytosis, low serum sodium, and elevated serum potassium due to extracellular shifting caused by insulin deficiency
  • 18. HYPERGLYCEMIC HYPEROSMOLAR NON KETOTIC SYNDROME (HHNS)?  Patients with HHNS present with severe hyperglycemia, profound dehydration, and some degree of alteration in mental status (50%). Typically patients have type 2 DM and mild renal impairment. The plasma glucose is frequently very elevated (> 600 mg/dL). Ketosis is usually only very mild or absent. Patients typically have severe dehydration, and plasma hyperosmolarity (> 340 mOsm/L) is one hallmark of this condition.
  • 19. HEMOGLOBIN A1C?  Hemoglobin A1c (glycohemoglobin) is glycosylated hemoglobin and is used as a measure of average serum glucose concentrations over the prior 2-3 months  Hemoglobin A1c is an overall indicator of glycemic control. It should be measured biannually in patients who meet treatment goals (typically A1c < 7%) or quarterly in patients whose therapy is actively changing. Although an ideal goal for A1c is < 7%, this goal must be individualized. Less intensive goals may be indicated in patients with frequent hypoglycemia, and more intensive goals may be desired in some patients to further reduce diabetes complications.
  • 20. CHRONIC COMPLICATIONS OF DM.  Microvascular  Neuropathy (painful paresthesia's, autonomic neuropathy)  Retinopathy (non proliferative and proliferative retinopathy, blindness)  Nephropathy (spectrum of disease from microalbuminuria to end- stage renal disease
  • 21.  Macrovascular  (cardiovascular and peripheral vascular disease)  Nonhealing ulcers, amputations  Hypertension  Dyslipidemia

Editor's Notes

  1. Causal is defined as anytime of day without regard to last meals. The classic symptoms of diabetes include polyuria,polydipsia,and unexplained weight loss.
  2. PG-PLASMA GLUCOSE