Hormonal Regulation - Diabetes Mellitus

Glucose

Preferred energy source for most cells in the body

Glycogen

Major form of stored glucose (primarily in liver), acts as fuel reserve for use in ATP synthesis

Glycogenolysis

Breakdown of Glycogen → Glucose

Gluconeogenesis

Process of producing glucose from non-carbohydrate sources (ex: proteins + fats), initiated by liver

Lipolysis

Triglycerides hydrolyzed to fatty acids + glycerol

Ketogenesis

Production of ketones from breakdown of fats

Normal Blood Glucose Levels (Fasting State)

70-99mg/dL

Normal Blood Glucose Levels (Post-Prandial)

100-140mg/dL

Insulin

Facilitates glucose metabolism (gets them into the cells so that we can use glucose): lowers blood glucose levels

Glucagon

Suppresses insulin and stimulates hepatic glucose production

Cortisol + Epinephrine + Norepinephrine

Stimulate use of glycogen stores and/or gluconeogenesis, stress response

Beta Cells (Pancreas)

Secrete Insulin

Alpha Cells (Pancreas)

Secrete Glucagon

Absorptive State

Shows what happens right after we eat, nutrients broken down to glucose and sent to cells to give energy

Post-Absorptive State

What happens when we are fasting (8+ hours of no food), glucose levels are lower in our bloodstream

Diabetes Mellitus

Group of disorders where the body’s ability to produce or response to insulin is impaired

Racial/Ethnic Groups (Risk Factors of Diabetes Mellitus)

Highest among American Indian/Alaskan Native population
Lowest among non-Hispanic white population

Population Groups (Risk Factors of Diabetes Mellitus)

Pregnant women, infants, lifestyle factors (high fat diet), older adults, family history

Diabetes Affects

1 in 10 adults in U.S.

Diabetes is the leading cause of…

Kidney failure, non-traumatic limb amputations, blindness, heart disease, stroke

Normal HgbA1C

<5.7%

Pre-Diabetes Glucose Levels (Fasting)

100-125mg/dL

Pre-Diabetes Glucose Levels (Postprandial)

141-199mg/dL

Pre-Diabetes Glucose Levels HgbA1C

5.7% - 6.4%

Diabetes Mellitus Glucose Levels (Fasting)

> 126mg/kL

Diabetes Mellitus Glucose Levels (Postprandial)

>200mg/dL

Diabetes Mellitus HgbA1C

> 6.5%

Gestational Diabetes

First diagnosed in pregnancy (recommended to screen at initial prenatal visit), recommended to monitor for diabetes after pregnancy → dietary treatment, possible oral medication + insulin

Risk Factors of Gestational Diabetes

Old maternal age, obesity, family history

Baby in Gestational Diabetes

Possible hypoglycemia after birth d/t increased insulin levels in response to mother’s high blood glucose

Absolute Insulin Deficiency

Requires exogenous insulin administration

Autoimmune Condition l/t Insulin Dependence

Type 1 Diabetes Mellitus (typically d/t environmental or genetic predisposition)

Type 1 Diabetes Mellitus

Lack of insulin secretion d/t t-cell mediated destruction of pancreatic beta cells (requiring lifelong insulin replacement therapy)

When is Type 1 DM typically diagnosed?

Childhood + Adolescence

Prediabetes

Impaired fasting glucose and/or impaired glucose tolerance → higher than normal glucose (not enough to diagnose DM): increases risk for developing type 2 DM

Type 2 Diabetes Mellitus

D/t insulin resistance + relative insulin deficiency developing over 3 stages (requiring insulin therapy or management)

Risk Factors of Type 2 DM

Family history, obesity, lack of physical activity, lower socioeconomic status

Greatest Risk Factor for Type 2 DM

Intra-Abdominal Obesity (increases risk by 10-fold)

Obesity’s Influence on Type 2 DM

Excess nutrients l/t increased insulin resistance + beta cell death (causing dyslipidemia + endothelial dysfunction + microalbuminuria)

Stage 1: Type 2 DM

Genetics influence insulin sensitivity + secretion, beta cells compensate to maintain normal glucose levels to increase insulin secretion

Stage 2: Type 2 DM

Beta cells are unable to keep up l/t high blood sugar levels staying high 2 hours post meals (normal fasting glucose remains)

Stage 3: Type 2 DM

Elevated normal fasting glucose l/t diagnosis

Hyperglycemia Manifestations

Polyuria, polydipsia, polyphagia, nocturia, glucosuria, hypotension, tachycardia, fatigue

Diabetic Ketoacidosis

Acute → Seen in Type 1 DM; patient does not secrete any insulin anymore (aka absolute/relative insulin deficiency)

Most Common Cause of Diabetic Ketoacidosis (DKA)

Underlying infection, disruption of insulin treatment, new onset of T1D

During DKA, what do ketone bodies develop into?

Ketonemia

Diabetic Ketoacidosis: Secondary Hypertriglyceridemia

FFAs → LDLs

DKA Diagnosis

Plasma Glucose > 250mg/dL, presence of ketonemia/ketonuria, acidosis

Hyperosmolar Hyperglycemic State (HHS)

Severe hyperglycemia but without ketosis or metabolic acidosis l/t dehydration, seizures, coma, vascular thrombosis

Diagnosis of HHS

Plasma Glucose Level >600, serum hyperosmolality >320, elevated BUN + creatinine

Hypoglycemia

D/t malnutrition, adverse reaction to medications, and excess exercise

Malnutrition

L/t depletion of glycogen stores

Excessive Exercise

L/t glucose stores quickly depleted with exercise

Neuroglycopenic Symptoms of Hypoglycemia

Dizziness, drowsiness, confusion, difficulty speaking, seizures

Later Symptoms of Hypoglycemia

Lack of glucose to brain l/t irritability, anxiety, seizures, death

Chronic Hypoglycemia

L/t decreased counterregulatory hormone response, hypoglycemic unawareness (most common in T1DM)

Neuropathy

Increased blood glucose levels l/t fructose + sorbitol accumulation in nerves l/t Na+ retention, edema, myelin swelling, nerve degeneration

Manifestations of Neuropathy

Gastroparesis (delayed emptying), diarrhea, constipation, neurogenic bladder, impotence, decreased libido, decreased SNS response to low blood sugar

Cataracts

Sorbitol deposits in lens or capsule l/t increased opacity

Glaucoma

Neovascularization blocks outflow AH l/t increased IOP

Nephropathy

Increased glucose l/t glomerular damage + basement membrane thickening (leading cause of end stage renal disease)

What is usually present during Nephropathy?

Hypertension (risk for nephropathy increases if patient has both diagnoses)

Infection Risk of Neuropathy

Decreased sensory perception of pain and motor function l/t increased injury

Infection Risk of Retinopathy

Decreased visual perception of tissue damage/risk

Infection Risk of Decreased Vascular Flow

Impedes release of O2 l/t hypoxia and ineffective cell function