ICL 3.2: Diagnostic Criteria, epidemiology and Pathophysiology of Diabetes

Question 1

what is diabetes?

Answer 1

a complete or relative lack of insulin

Question 2

how many people have prediabetes?

Answer 2

84. 1 million adults aged 18 years or older have prediabetes which is 33.9% of adults in the US!
85. 1 million adults over 65 or older have prediabetes

Question 3

how many people have diabetes?

Answer 3

30.3 million which is 9.4% of the US population

only 23.2 million are diagnosed though so 7.2 million are undiagnosed = 1/4 people with DM don’t know they have it

Question 4

what are the types of diabetes?

Answer 4

1. type I
2. type II
3. gestation DM
4. specific types of DM due to other causes

Question 5

is type I and II totally separate?

Answer 5

no

people can’t be clearly classified as type 1 or 2

traditional paradigms of type 2 diabetes occurring only in adults and type 1 diabetes only in children are no longer accurate, as both diseases occur in both age-groups

Question 6

how common is type I DM?

Answer 6

5-10% of DM

In the US, incidence in non-Hispanic white children and adolescents is 23.6 per 100,000 per year, and rates are substantially lower in other racial or ethnic groups

commonly occurs in childhood & adolescence. Can occur at any age, even in 8th and 9th decades of life

Question 7

what is the cause of type I DM?

Answer 7

cellular mediated autoimmune destruction of pancreatic B cells

Question 8

what are the autoimmune markers for DMI?

Answer 8

1. islet cell autoantibodies
2. autoantibodies to GAD (GAD65), insulin, the tyrosine phosphatases IA-2 and IA-2β, ZnT8

must have 1 or more autoimmune markers to be considered DMI

Question 9

what is the HLA associated with DMI?

Answer 9

specific HLA DR3, DR4 haplotypes confer increased risk

DQB1 *0602 allele confers reduced risk

Question 10

what is the initial presentation of DMI?

Answer 10

in children, they present with DKA but with adults it’s more variable

adults may retain Adults may retain sufficient β-cell function to prevent DKA for many years however….they are prone to other autoimmune disorders so you need to screen them for those too (Hashimoto thyroiditis, Graves, Addison, etc.)

Question 11

what is the mechanism of insulin secretion?

Answer 11

glucose is taken up by GLUT2 transporter to the pancreatic B cell where it enters the Kreb cycle and makes ATP

ATP then inhibits K+ channels which inhibits K from leaving the cell and this results in depolarization of the cell membrane and the entrance of Ca into the cell

increased intracellular Ca leads to fusion of insulin vesicles with the membrane and release of insulin from the cell

Question 12

what is the structure of insulin?

Answer 12

it’s a peptide hormone that comes from proinsulin precursor

C-peptide and insulin are both formed and so when you measure pancreatic B cell function you measure C-peptide because it isn’t broken down by the liver like insulin is

Question 13

what is the effect of insulin on adipose?

Answer 13

1. increase glucose uptake
2. increase lipogenesis
3. decrease lipolysis

Question 14

what is the effect of insulin on muscle?

Answer 14

1. increased glucose uptake
2. increased glycogen synthesis
3. increased protein synthesis

Question 15

what is the effect of insulin on liver?

Answer 15

1. decreased gluconeogenesis
2. increased glycogen synthesis
3. increased lipogenesis

Question 16

how common is type II DM?

Answer 16

9% of US population has type II DM

6% worldwide prevalence but undetected may be as high as 50%

type II DM account for over 90% of patients with diabetes

Question 17

what is the cause of type II DM?

Answer 17

progressive loss of B cell insulin secretion frequently on the background of insulin resistance

primarily associated with insulin secretory defects related to:

1. inflammation
2. metabolic stress
3. genetic factors

Question 18

what is the pathophsyiolgo of type II DM?

Answer 18

1. insulin resistance
2. B cell dysfunction

progressive insulin resistance leads to decreased glucose uptake by the muscles and fat which leads to increased glucose output by the liver resulting in hyperglycemia and the pancreas secretes even more insulin

Question 19

why does the B cell fail in type II DM?

Answer 19

in the beginning of DM, the pancreas is trying to compensate for insulin resistance and so it’s making up for it by over producing insulin

over time this mechanism will fail and glucose will increase which leads to glucotoxicity and the super high levels of glucose actually suppress the pancreas from secreting insulin

so you have to treat these patients with exogenous insulin so the pancreas can have a break and recover

Question 20

which DM is DKA common in?

Answer 20

type I DM

Question 21

A 39-year-old woman comes to the physician for an annual health maintenance examination. On questioning, she has had fatigue and headaches for the last month. She has mild persistent asthma and anxiety disorder. She drinks 2-3 glasses of red wine per night and has smoked one pack of cigarettes daily for 16 years. She works a desk job in accounting. She has gained weight the last few months. Current medications include alprazolam, a fluticasone inhaler, and an albuterol inhaler.
She is 160 cm (5 ft 3 in) tall and weighs 81.6 kg (180 lb); her BMI is 32 kg/m2. Her temperature is 37.2°C (99°F), pulse is 92/min, and blood pressure is 132/80 mm Hg. Examination shows no abnormalities.Glucose 160.

which of the following is the most likely underlying mechanism of the patient’s hyperglycemia?

Answer 21

insulin resistance and subsequent pancreatic B cell dysfunction

she probably has type II DM

BMI is high and she’s 39

Question 22

what is the diagnostic fasting glucose for DM?

Answer 22

over 126 mg/dL

Question 23

what is the clinical presentation of DM?

Answer 23

1. chronic polydipsia
2. polyuria
3. weight loss with hyperglycemia and ketonemia
4. DKA
5. silent; could be asymptomatic

Question 24

what does an insulin deficiency/resistance result in pathophysiologically?

Answer 24

decreased tissue glucose uptake, increased glycogenolysis and increased gluconeogeisis lead to hyperglycemia – this increases plasma osmolatility which results in increased thirst – it also results in osmotic diuresis which results in loss of water, Na and K with hypovolemia, circulation failure, decreased tissue perfusion and potentially coma/death

insulin deficiency also results in increased proteolysis resulting gin decreased protein and weight loss

there’s also increased lipolysis which increases plasma free FA resulting gin increased ketogenesis and subsequently DKA – increased ketogeneis also can result in vomiting

Question 25

what is the criteria for diagnosis of DM?

Answer 25

1. fasting plasma glucose ≥ 126 mg/dl – fasting is defined as no caloric intake for at least 8 hours.
2. 2-h plasma glucose ≥ 200 mg/dl during OGTT

test should be performed as described by the WHO, using glucose load containing equivalent of 75-g anhydrous glucose dissolved in water.

3. A1c ≥ 6.5%
4. patient with classic symptoms of hyperglycemia OR hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dl

in the absence of unequivocal hyperglycemia, diagnosis requires 2 abnormal test results from the same sample OR in 2 different test samples.

Diabetes type 1: above criteria + presence of ≥1 autoimmune markers

Question 26

what is the criteria for prediabetes?

Answer 26

individuals whose glucose levels do not meet criteria for diabetes but are too high to be considered normal

should not be viewed as a clinical entity, but rather as an increased risk for diabetes & CV disease

criteria defining prediabetes:
1. fasting plasma glucose 100-125 mg/dl [impaired fasting glucose (IFG)]

2. 2-h plasma glucose during 75-g OGTT, 140-199 mg/dl [impaired glucose tolerance (IGT)]
3. A1c 5.7-6.4%

Question 27

what is gestational DM?

Answer 27

DM diagnosed int eh 2nd or 3rd trimester of pregnancy that was not clearly overt diabetes prior to gestation

test at 24-28 weeks gestation in pregnancy women not previously know to have DM

test women with GDM for prediabetes/diabetes 4-12 weeks postpartum, using 75-g OGTT and clinically appropriate non-pregnancy diagnostic criteria

lifelong screening at least every 3 years

Question 28

what is the pathophysiology of gestational DM?

Answer 28

pregnancy – accompanied by insulin resistance, mediated by placental secretion of diabetogenic hormones including:

1. GH
2. CRH
3. placental lactose
4. prolactin
5. progesterone

Question 29

what is the etiology of gestational DM?

Answer 29

hormonally induced insulin resistance resulting in hyperglycemia and eventually progresses into GDM

Question 30

what are the risk factors for GDM?

Answer 30

1. obestiy
2. previous history of GDM
3. prior delivery of a large baby
4. glycosuria
5. family history of DM in first degree relative

Question 31

how is GDM related to DMII?

Answer 31

5%-10% of women with GDM develop T2DM immediately postpartum

35%-60% chance of T2DM over next 10-20 years

risk increased with uncontrolled blood sugar in pregnancy5

Question 32

what are the maternal risk assaocied with GDM?

Answer 32

1. preeclampsia

2. 30% mortality rate

Question 33

what are the fetal risk assaocied with GDM?

Answer 33

1. macrosomia
2. shoulder dystocia
3. increased congenital malformations

Question 34

how do you screen for GDM?

Answer 34

step 1: 50 g OGTT, non fasting

if 1 hr >140 mg/dL then proceed to step 2 which is 100 g OGTT fasting test

nowadays you just give 75 g OGTT at 24-28 weeks and you can diagnose if:

1. fasting over 92
2. 1 hr > 180
3. 2 hr >153

Question 35

A 24-year-old woman gravida 2, para 1 at 24 weeks’ gestation comes to the physician for a prenatal visit. She feels well. Her earlier pregnancy was uncomplicated. This is her 4th prenatal visit. She had an ultrasound scan 2 weeks ago that showed a live intrauterine pregnancy consistent with a 22-week gestation with no anomalies. She had a normal Pap smear 2 years ago.

Vital signs are within normal limits. Pelvic examination shows a uterus consistent in size with a 24-week gestation. Her blood group and type is B positive.

what is the most appropriate next step in management?

Answer 35

OGTT

screen for gestational DM so a 50 g one hour oral glucose challenge test is recommended for every pregnant women at 24-28 weeks

a positive screening test should be followed by a diagnostic 100-g, three- hour oral glucose tolerance test

early diagnosis and treatment of gestational diabetes mellitus are important to avoid potential complications of this condition, including hypertension, preeclampsia, macrosomia, and shoulder dystocia

Question 36

what are the glycemic targets for pregnancy women with DM?

Answer 36

1. fasting <95
2. 1 hr postprandial <140
3. 2 hr postprandial <120

with nonpregnant adults with DM the goal is:

1. A1c < 7
2. preprandial capillary plasma glucose 80-130
3. peak postprandial capillary plasma glucose <180

Question 37

what are other causes of DM?

Answer 37

1. monogenic diabetes syndromes: neonatal diabetes or maturity-onset diabetes of the young
2. diseases of the exocrine pancreas: CF and pancreatitis
3. drug or chemical induced diabetes like glucocorticoid use, thiazide diuretics, treatment of HIV/AIDS, or after organ transplant
4. secondary to other endocrinopathies like Cushing’s syndrome or acromegaly

Question 38

how is CF related to DM?

Answer 38

annual screening by age 10 via OGTT with anybody with CF!

A1c is not recommended and you treat then with insulin because pancreas is effected

Question 39

what is MODY?

Answer 39

maturity onset diabetes of the young that is a genetic defect in B cell function

AD inheritance

manifests before age 25

not associated with obesity or autoantibodies

most common cause is MODY2: defect in glucokinase and MODY3: defect in hepatocyte nuclear factor 1α

Question 40

A 20-year-old female presents for routine physical examination. She feels well. She is 163 cm (5ft 4in) tall and weighs 54 kg (120lb); BMI is 21 kg/m2. Physical examination shows no abnormalities.

fasting serum glucose: 132 mg/dL

serum insulin concentration 30 minutes after oral glucose administration is 20ml U/L (N= 30-230)

A1C concentration is 7.1%

After a thorough workup, the physician concludes that the patient has a chronic condition that can likely be managed with diet only and that she is not at a significantly increased risk of micro- or macrovascular complications.

which of the following is the most likely cause of the patient’s condition?

Answer 40

defect in expression fo glucokinase aka MODY type II

she’s under 25 and diabetic but BMI is normal however low serum insulin concentration

she also has no complications of the DM which is common in MODY

it’s not MODYIII because it has glucose complications

Question 41

what is MODY II?

Answer 41

defect in glucokinase causes increase in the threshold of glucose required to promote insulin secretion

manage with dietary modification only as medical treatment fails to lower glucose and A1c

not at risk for micro or microvascular complications despite mild fasting hyperglycemia and chronically elevated A1c