Diabetes lecture 1 Flashcards
Type 1 diabetes
autoimmune β-cell destruction, usually leading to absolute insulin deficiency
Type 2 Diabetes
progressive loss of β-cell insulin secretion frequently on the background of insulin resistance
Gestational diabetes (GDM)
diabetes that is first diagnosed in the 2nd or 3rd trimester that is not clearly preexisting type 1 or type 2 diabetes
Other causes of diabetes
Genetic defects
Disease of the exocrine pancreas (cystic fibrosis, pancreatitis)
Drug-induced hyperglycemia
Pathophysiology of Type 1
-Defect in pancreatic β-cell function»_space; deficiency of insulin
and amylin
-Relative increase in glucagon – disequilibrium is created
with insulin
-Increase in BG fails to suppress production of glucagon
-Effects metabolism of fat, protein, and CHOs
-Protein and fat breakdown occurs because of lack of insulin
– results in weight loss
-Ketoacidosis will result if no treatment
Type 1
decreased insulin leads to increase glucose
glycogen and protein breakdown cause keto-acidosis
Stages of Type 1
Stage 1: autoimmune, normoglycemic, pre-symptomatic
Stage 2: Autoimmune, dysglycemic, pre-symptomatic
Stage 3: Autoimmune, hyperglycemia, symptomatic
Rate of progression of Type 1 is dependent on
Age at first detection
Number of autoantibodies
Autoantibody specificity
Autoantibody titers
Pathophysiology of Type 2
Genetic predisposition and lifestyle –> insulin resistance –> B cell decompensation –> insulin resistance and B cell failure
Factors of Type 2 leading to hyperglycemia
impaired insulin secretion in pancreas increased glucagon secretion in pancreas increased HGP in liver Neurotransmitter dysfunction in brain decrease glucose uptake in muscles increased glucose reabsorption in kidney increase lipolysis in adipose tissue decreased incretin effect in gut
metabolic defects:
Insulin resistance in muscle
ineffective glucose uptake
metabolic defects:
Insulin resistance in liver
increase glucose secretion
metabolic defects:
Pancreatic B cell decline
reduced insulin secretion
metabolic defects:
increased activity of a-cells in the pancreas
higher blood levels of glucagon increase blood glucose levels
metabolic defects:
Increased free-fatty acid levels in the blood from fat cell breakdown
more insulin resistance, toxic to beta-cells
metabolic defects:
Loss of incretin function from the gut
deficiency/resistance
metabolic defects:
Sodium-glucose cotransporter upregulation in the kidney
results in higher blood glucose levels
Risk factors of Type 1
Genetic Environmental (poorly defined)
Risk factors Type 2
BMI ≥ 25 kg/m2 (≥ 23 kg/m2 in Asian Americans) Physical inactivity Hypertension HDL < 35 mg/dL and/or TG > 250 mg/dL First degree relative with diabetes Women who were diagnosed with GDM Women with polycystic ovary syndrome High risk race/ethnicity Prediabetes on previous testing History of CVD
gestational Diabetes risk factors
overweight
older age
family history of type 2
gestational diabetes pathophysiology
insulin resistance
diminished insulin secretory response
Gestational diabetes risks to mother and baby
Macrosomia Shoulder dystocia Preeclampsia Cesarean delivery Stillbirth
Clinical manifestations of hyperglycemia
Polyuria (excessive urination)
Polyphagia (excessive hunger)
polydipsia (excessive thirst)
Factors that decrease glucose
insulin
excess DM medications
increased exercise
alcohol
Factors that increase glucose
counter-regulatory hormones insufficient DM medications other medications excess food illness stress
Screening for Type 1
Autoantibodies
- Islet cell (ICA)
- Glutamic acid decarboxylase (GAD65)
- Insulin autoantibodies (IAA)
- Tyrosine phosphatases (IA-2 and IA-2β)
- Zinc transporter 8 (ZnT8)
Screening for Type 2
- Starting at age 35
- Anyone obese (BMI> 25 or >23 in Asian americans) plus 1 more riks factors
- people with HIV
- pre-diabetics
- Women with GDM
With normal results, repeat screening for Type 2 every
3 years
if results indicate pre-diabetes, repeat type 2 screening
yearly
Fasting plasma glucose
no caloric intake for at least 8 hours
OGTT
75 g anhydrous glucose dissolved in water
Diagnoses more patients than A1C or FPG
Hemoglobin A1C
- Reflects glycemic control over previous 2-3 months
- Strong predictive value for complications
- Advantages of A1C compared to FPG and
OGTT:
- Greater convenience (fasting not required)
- Less day-to-day variations during periods of stress or illness
Testing for Diabetes
FPG
Casual plasma glucose
OGTT
A1C
Hemoglobin A1C
Percent glycosylation of
hemoglobin subfraction, A1c
Binding of glucose to hemoglobin A
is a nonenzymatic process that
occurs over the lifespan of a red
blood cell
limitations of A1C
A1C inaccurately reflects glycemia in conditions that alter red blood cell turnover
o Sickle cell disease
o Pregnancy
o Glucose-6-phosphate dehydrogenase deficiency
o End stage renal disease
o Recent blood loss or transfusion
o Hemodialysis
Testing for Type 1
Same blood tests as type 2 diabetes
Presence of 2 or more autoimmune markers
Plasma glucose rather than A1C preferred in acute onset
C-peptide useful to differentiate type 1 from type 2
o Levels generally match insulin levels
o Low levels usually = type 1 diabetes
Diagnosis Criteria for A1C
pre = 5.7-6.4%
diabetes = > 6.5%
Diagnosis Criteria for FPG
Pre = 100-125 mg/dL
diabetes = > 126 mg/dL
Diagnosis Criteria for OGTT
pre = 140-199 mg/dL
diabetes = > 200 mg/dL
Diagnosis Criteria for random glucose
Diabetes = ≥ 200 mg/dL plus classic
symptoms of hyperglycemia
or hyperglycemic crisis
FGP and PPG to A1C
Higher the A1C, less contribution of PPG, more FPG
Goals therapy
Attain normoglycemia (or appropriate glycemic control)
Reduce onset and progression of diabetes-related complications
Aggressively address CV risk factors
Improve quality and quantity of life
A1C goal
< 7%
preprandial glucose (fasting) goal
80-130 mg/dL
peak postprandial glucose
< 180 mg/dL
made 1-2 hours after the beginning of meal
Children and adolescents
less stringent goals to minimize risk of hypoglycemia
Goals for pediatrics type 1
A1C = <7.5% fasting = 90-130mg/dL bedtime/overnight = 90-150mg/dL
Diagnostic criteria for pregnant women using 75-g fasting OGTT
Fasting >92mg/dL
1 hour >180 mg/dL
2 hour >153 mg/dL
target glucose range for hospitalized patients
140-180 mg/dL
Goals for older adults (healthy)
A1C = < 7-7.5% Preprandial = 80-130 mg/dL Bedtime = 80-180 mg/dL
Goals for older adults (complex/intermediate)
A1C = < 8% Preprandial = 90-150mg/dL Bedtime = 110-200 mg/dL
Goals for older adults (very complex/poor health)
A1C = < 8.5% Preprandial = 100-180 mg/dL Bedtime = 110- 200 mg/dL
