Endo E1- Glucose Intolerance

What is the main regulator of blood sugar?

Insulin

What pattern do basal insulin levels follow?

low and constant overnight and between meals, allowing the body to release sugar and other fuels from the liver

In healthy individuals, what do blood sugar levels peak at after eating before falling back to baseline?

<140 mg/dL

What is considered a normal blood sugar level?

60-100

In healthy individuals, when is glucagon released?

Overnight & Between meals

What are incretin hormones?

GLP-1 & GIP

What effect do incretin hormones have on beta cells?

Increase insulin secretion

What effect do incretin hormones have on alpha cells?

Decrease glucagon secretion

What is the role of GLP-1?

slows down stomach emptying and acts on the brain to make you feel full

Diabetics have (increased/decreased) GLP-1

Decreased

What hormone is released along with insulin and has nearly the same effect as GLP-1?

Amylin

What is the overall effect of GLP-1, GIP, & amylin?

reduce sugar production by liver during meals

What are "Gluco-counter-regulatory" hormones?

Epi, Cortisol, GH, Glucagon

If under stress, cortisol levels become elevated and you can become what?

Insulin resistant

Which type of diabetes is associated with HLA?

Type 1A DM

What type of diabetes is an “Absolute insulin deficiency”?

T1DM

What causes Type 1A DM?

Cellular-mediated autoimmune destruction of the beta cells of the pancreas

What is the pathogenesis behind T1DM?

Stress-induced epi release → insulin inhibited → honeymoon period → permanent diabetes

T1DM pts are completely deficient in what?

both insulin AND amylin

What is Type 1B DM?

Idiopathic diabetes without evidence of autoimmunity or HLA association

In T2DM, insulin secretion is initially (high/low), eventually leading to insulin resistance

High

In T2DM, insulin resistance leads eventually leads to what?

relative deficiency

Do genetics play a stronger role in T1DM or T2DM?

T2DM

What are the components of metabolic syndrome associated with T2DM/Glucose intolerance?

Insulin resistance, Hyperinsulinemia, Obesity, HTN, Dyslipidemia

What may further impair insulin secretion by beta cells in pts with T2DM?

glucose toxicity & lipotoxicity

What are the 4 factors that affect blood glucose levels?

Carb intake, Hepatic glucose production, Pancreatic insulin secretion, Peripheral glucose uptake

Do all overweight individuals have insulin resistance?

Yes

What hormones are insulin antagonists in gestational DM and work to promote lipolysis and dec glucose use?

Human placental lactogen (AKA chorionic somatomammotropin) and cortisol

What enzyme is produced by the placenta in response to increased insulin requirements during pregnancy?

Insulinase

What is dipeptidyl peptidase (DDP-4)?

Major enzyme responsible for degrading incretin hormones in vivo

Glucose intolerance/T2DM can cause __________ hyperglucagonemia

Postprandial

(T1DM/T2DM) is reaching epidemic proportions

T2DM

Diabetes is the leading cause of what conditions?

End-stage renal disease & Blindness

Gestational DM has a high risk of what obstetric complication?

Shoulder dystocia

What is the most consistent predictor of progression from pre-diabetes to diabetes?

Baseline plasma glucose

Pre-diabetes puts patients at increased risk of (macrovascular/microvascular) complications even prior to developing T2DM

Macrovascular

What races have the highest risk for glucose intolerance?

Native Americans and Pacific islanders

Is impaired glucose tolerance more common in women or men?

Women

Is diabetes more prevalent in women or men?

No consistent trend

While childhood and adolescent cases are increasing, T2DM usually beings after what age?

30

What are warning sx of T1DM?

polyuria, polydipsia, polyphagia; unexplained wt loss and easy fatigue

What is a Hyperosmolar nonketotic coma characterized by?

severe dehydration secondary to osmotic diuresis from hyperglycemia

What is Prediabetes?

categories of impaired glucose tolerance and impaired fasting glucose

What is DKA?

Overt hyperglycemia that has progressed to diabetes, resulting in signs of dehydration (hypotension, hemodynamic compensation, worsening hyperglycemia)

What are clinical signs of DKA?

Kussmaul respirations & altered level of consciousness

What is the most common cutaneous finding in DM?

Diabetic dermopathy (shin spots)

What is Diabetic dermopathy (shin spots)?

Round/oval atrophic hyperpigmented macules to the pretibial areas bilaterally

What is Xanthoma eruptiva?

Pink papules with "creamy" center due to elevated TRGs, usually seen in diabetes on extensor surfaces & popliteal region

What is Necrobiosis lipodica diabeticorum?

Degenerative disease of collagen that presents as atrophic, waxy telangiectatic plaques that ulcerate or fluid filled bullae typically associated w/ peripheral neuropathy

What may be the first presentation of elevated glucose?

repeated yeast infections(Candidiasis)

What is Kyrle's disease (AKA reacting perforating collagenosis)?

Pruritic papules with keratotic plug on the extensor surfaces of legs (may also affect face/arms); typically associated with kidney disease

What study is the preferred diagnostic test for DM per the ADA?

Fasting plasma glucose

The standard oral glucose tolerance test (OGTT) involves measurement of plasma glucose ___ hours after a 75g oral glucose load

2

Diabetes HBA1C:

> 6.5%

Pre-diabetes HBA1C:

5.6-6.4%

Normal HBA1C:

< 5.6%

Normal OGTT result:

Glucose <140 mg/dL

Pre-diabetes fasting plasma glucose:

100-125 mg/dL

Pre-diabetes 2-hour OGTT result:

140-199 mg/dL

Diabetes fasting plasma glucose

> 126 mg/dL

Random plasma glucose ______ = diabetes

> 200 mg/dL

2-hour OGTT of ______ = diabetes

> 200 mg/dL

When should screening for T2DM should be considered?

at 3 year intervals in all individuals over age 45

For diagnosis of T2DM in children, the child must be >85th percentile, plus 2/4 risk factors. What are the 4 risk factors?

1. FHx of T2DM

2. High risk race/ethnicity

3. Signs of insulin resistance

4. Maternal hx of DM/gestational DM

When screening for gestational diabetes, at what intervals should you perform a 75g OGTT?

Fasting, 1 hr, 2 hr

When should patients should be screened for gestational DM?

24-28 weeks gestation

How often should women with gestational DM should be screened for persistent DM?

6-12 weeks postpartum, then every 3 years

What urinalysis findings are indicators of acute decompensation in a diabetic patient?

Ketonuria & Massive glycosuria

What urinalysis finding is a marker of early renal impairment and endothelial dysfunction?

Urine microalbumin

LFTs are necessary to assess baseline function prior to starting which antihyperglycemic medications?

Biguanides, TZDs

*continue periodic LFTs w/ TZDs

What lipid panel findings might be seen in a diabetic pt?

Elevated TRGs, Increased cholesterol, LDLs

What is a CBC finding in a patient with ketoacidosis?

Leukocytosis

What is the major goal in the management of glucose intolerance?

Glycemic control

What diet is recommended as lifestyle modification for diabetic patients?

Mediterranean

What is the minimum amount of activity recommended for lifestyle modifications for a diabetic patient?

150 mins/week of moderate exercise

How is Gestational DM treated?

insulin ± lifestyle changes

*oral agents are CI in pregnancy

Bariatric surgery is recommended for patients with a BMI >______

35

At what levels of fasting glucose, OGTT, and HbA1C should pharmacologic therapy be considered?

Fasting glucose >126

OGTT >160

HbA1C > 7%

What is the first drug of choice for oral T2DM treatment?

Metformin

What is the primary effect of metformin?

Decrease hepatic gluconeogenesis

What is the CI for metformin?

Renal impairment

Which sulfonylurea has the longest half life?

Glyburide (Diabeta, Glynase)

What sulfonylurea has the lowest risk for hypoglycemia and weight gain?

Glipizide (Glucotrol)

What drug classes are secretagogues (stimulate insulin release from pancreas)?

Sulfonylureas & Meglitinides

What drug class slows digestion & absorption of carbs in the GI tract?

Alpha-glucosidase inhibitors (Acarbose, Miglitol)

What drug class causes lots of bowel gas?

Alpha-glucosidase inhibitors (Acarbose, Miglitol)

Which TZD is linked to slightly increased risk for bladder cancer?

Pioglitazone (Actos)

What is the MOA of TZDs?

Reduce insulin resistance in fat and muscle

What drug class is injected SC and promotes moderate weight loss?

GLP-1 agonists

What drug class inactivates the major enzyme responsible for degrading incretin hormones, prolonging the action of incretins?

DDP-4 inhibitors

-glutide

GLP-1 agonists

-gliptin

DDP-4 inhibitors

What drug class increases urinary glucose excretion by lowering the renal glucose threshold?

SGLT-2 inhibitors

-gliflozin

SGLT-2 inhibitors

What drug class mimics an endogenous hormone by delaying gastric emptying, decreasing postprandial glucagon release, and modulating apetite?

Amylin analogue (Pramlintide aka SymlinPen)

What macrovascular complications may arise from prediabetes/diabetes?

CAD, PVD, stroke

What microvascular complications may arise from diabetes?

Retinopathy, Neuropathy, Nephropathy, Acute metabolic conditions