Far Eastern University – Nicanor Reyes Medical Foundation
IM 3B: DIABETES MELLITUS AND HYPOGLYCEMIA
DIABETES MELLITUS
CASE 1
- 35-year old male
- progressive weight loss, frequent urination at night
- (+) family history of diabetes mellitus
- PE is unremarkable
CASE 2
- 52 year-old male
- Type 2 DM for 10 years
- Glycated hemoglobin - 12%
- Medications: Metformin 500 mg TID
ETIOLOGIC CLASSIFICATIONS OF DIABETES MELLITUS
- Type 1 Diabetes Mellitus
- Type 2 Diabetes Mellitus
- Gestational Diabetes
- Specific types of diabetes due to other causes
INTERNAL MEDICINE 3B: DIABETES MELLITUS AND
HYPOGLYCEMIA
GESTATIONAL DIABETES MELLITUS
- Glucose intolerance that develops during the second or
Dr. Custodio third
- trimester of pregnancy
- Diabetes diagnosed within the first trimester is classified as
preexisting pregestational diabetes - ADA
- ADA recommends women with history of GDM undergo
lifelong screening for the development of diabetes or
prediabetes at least every 3 years
TYPE 1 DIABETES
- Interaction of genetic, environmental and immunologic
factors leading to destruction of the pancreatic beta cells
and insulin deficiency
- Features of diabetes become evident when 70-80% of the
beta cells are destroyed
- Develops mostly before 20 years old but can develop at any
age
- Most but not all have evidence of islet-directed
autoimmunity
TYPE 2 DIABETES
- Genetic susceptibility and environmental factors (obesity,
nutrition and physical activity)
- Strong genetic component: if both parents have type 2 DM,
the risk approaches 40%
- Obesity is very common in T2DM (>80%)
- Beta cell is reduced by as much as 50% at the onset
MONOGENIC FORMS OF DM
- MODY 1 - mutation in HNF 4a
- MODY 2 - mutation in glucokinase
- MODY 3 - mutation in HNF 1a
- MODY 4 - mutation in pancreatic and duodenal homeobox
1
- MODY 5 - mutation in HNF 1b
EPIDEMIOLOGY
- 1985 - 30 million of cases
- 2017 - 415 million of cases
- 2040 - 642 million of cases
CRITERIA FOR THE DIAGNOSIS OF DM
- Symptoms of diabetes + RBS > 11.1 mmol/L OR
- FPG > 7 mmol/L OR
- HgA1c > 6.5% OR
- 2-H plasma glucose >11.1 mmol/L during OGTT
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 SPECTRUM OF GLUCOSE HOMEOSTASIS

GLUCOSE HOMEOSTASIS

PATHOGENESIS
- TYPE 1 DM
o Result of interactions of genetic, environmental and
immunologic factors -> immune mediated destruction
of pancreatic beta cell and insulin deficiency
o Develops at any age - most common before 20 years
of age

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 o The concordance of T1DM in identical twins is
between 40-60% o Diabetes Prevention Study
o Most individuals with T1DM (75%) dont have first § Intensive lifestyle modification VS Metformin VS
degree relative with the disease § Placebo: (58%; 31% vs placebo)
o Most will have evidence of islets autoimmunity o ADA suggest the use of metformin in individuals with
o Major susceptibility gene is located in the HLA region both IFG and IGT who are very high risk for the
of chromosome 6 development of diabetes mellitus
o Most individual with type 1 DM have HLA DR3 and/or
DR4 haplotype APPROACH TO PATIENT
o ICA - GAD, insulin, IA-2/ICA 512, ZnT-8 - HISTORY
o ICA - present in >85% of individual who are newly o weight changes
diagnosed with T1DM, 5-10% of newly diagnosed o family history of DM and its complications
T2DM o sleep history
o and <5% in GDM o risk factors for CVD
- Type 2 DM o exercise
o Insulin resistance and abnormal insulin secretion are o smoking and alcohol intake
central to the development of type 2 DM o symptoms of hyperglycemia
o It has a strong genetic component o symptoms of complications
o Concordance in identical twin is between 70-90% o if diagnosis is already established - initial signs and
o If both parents have diabetes, the risk approaches 40% symptoms
o The disease is polygenic and multifactorial o history of treatment
o The genes that predisposes to T2DM are incompletely o associated complications
identified o frequency of hypoglycemia
o Insulin resistance - decrease glucose utilization and o patient’s knowledge
increase hepatic glucose output o Pregnancy plans
- PHYSICAL EXAM
o weight,BMI
o retinal examination
o orthostatic BP
o foot exam
o peripheral pulse
o insulin injection sites
o teeth and gums
o annual foot exam
- CLASSIFICATION
TYPE 1 TYPE 2
- Beta cell production, - insulin resistance with
absolute insulin insulin deficiency to
deficiency insulin secretory defect
- onset prior to age 30 with insulin resistance
- lean body habitus - onset after the age 30

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 complications
- requires insulin as initial - 80% obese
- Manage or treat diabetes relevant conditions
therapy - may not require insulin
- propensity to develop as initial therapy
acidosis - may associated DIABETES SELF- MANAGEMENT EDUCATION
- increased risk for other conditions such as - To provide patient centered individualized education
conducted by diabetes educator
autoimmune disease insulin resistance, HPN,
CVD, PCOS
NUTRITIONAL RECOMMENDATION
- LABORATORY ASSESSMENT
- Medical Nutritional therapy - term used by ADA to describe
o Confirm the diagnosis of DM
the optimal coordination of caloric intake with other
o Assess glycemic control
aspects of diabetes therapy
o Screen for DM associated condition
- General dietary guidelines
o vegetables, fruits, whole grains, legumes, low fat dairy
GLYCEMIC CONTROL
products in food higher in fiber and lower in glycemic
HbA1c <7%
content
Preprandial CPG 4.4-7.2 mmol/l
- Fat in diet - individualized
Postprandial CPG <10 mmol/L
- Carbohydrate in diet - individualized
BP <140/90 mmHg
- Protein in diet – individualized
- Others:
GUIDELINES FOR ONGOING, COMPREHENSIVE MEDICAL CARE o reduced calorie and nonnutritive sweeteners may be
FOR PATIENTS WITH DIABETES used
- Individualized glycemic goal and therapeutic plan o routine supplements - not supported by evidence
- Self monitoring of blood glucose (Individualized frequency) o sodium intake as advised to general population
- HbA1c testing (2-4 times/year)
- Lifestyle management in the care of diabetes
- Detection, prevention or management of diabetes related

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 PHYSICAL ACTIVITY PROPERTIES OF INSULIN PREPARATIONS
- ADA recommends 150min/week of moderate aerobic
- physical activity, distributed over at least 3 days, with no
gaps longer than 2 days
- Resistance exercise, flexibility and balance training and
reduced sedentary behaviour throughout the day are
advised.

MONITORING THE LEVEL OF GLYCEMIC CONTROL

- Self monitoring blood glucose
o Type 1 DM or Type 2 DM on multiply injections - 3 or
more times a day
o Assess short term glycemic control
- Glycated hemoglobin
o Assess long term glycemic control
o ADA recommends at least 2x a year measurement of
HgA1c

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 tachycardia and altered mental status
- Underlying cause: relative insulin deficiency and poor oral
intake

ACUTE DISORDERS RELATED TO SEVERE HYPERGLYCEMIA

DIABETES KETOACIDOSIS
- Signs and symptoms of DKA develops over 24 hours.
o Nausea, vomiting, abdominal pain, symptoms of
hyperglycemia, dehydration, Kussmaul’s respiration
- DKA results from relative or absolute insulin deficiency
combined with counterregulatory hormone excess
- It is characterized by hyperglycemia, ketosis and metabolic
acidosis

HYPERGLYCEMIC HYPEROSMOLAR STATE

- Elderly patients with several week history of
hyperglycemia,
- and decrease intake that culminates in mental confusion,
- lethargy and coma.
- PE: profound dehydration, hyperosmolality, hypotension,

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MANAGEMENT OF DIABETES IN HOSPITALIZED PATIENT
- Hyperglycemia - predictor of poor outcome in hospitalized
patients
- The goals for management is near-normoglycemia,
avoidance of hypoglycemia and transition back to the
outpatient diabetes treatment regimen
- Glycemic goals
o critically and non critically ill patients - 140-180 mg/dl
o selected group of patients - 110-140mg/dl with
avoidance of hypoglycemia
DIABETES COMPLICATIONS
RENAL COMPLICATIONS OF DM
FEATURES OF DIABETES COMPLICATIONS
- Duration and degree of hyperglycemia
- Intensive glycemic control is beneficial in all forms of DM
- BP control is critical especially in type 2 DM
- Survival in patient with T1DM is improving, and diabetes
related complications are declining
- Not all individuals with diabetes develop diabetes-related
complications
INTERNAL MEDICINE 3B: DIABETES MELLITUS AND
HYPOGLYCEMIA
OPHTHALMOLOGIC COMPLICATIONS OF DM
- DM is the leading cause of blindness between the ages 20
and 74 in US
- 2 stages of diabetic retinopathy
o Nonproliferative - late first decade to early second
decade of disease; with retinal vascular
microaneurysm, blot hemorrhages and cotton wool
spots.
o Proliferative - neovascularization -> vitreous
hemorrhage, fibrosis and retinal detachment
- Pathophysiology
o Nonproliferative
§ loss of retinal pericytes
§ increased retinal vascular permeability
§ alterations in retinal blood flow
§ abnormal retinal microvasculature
o Proliferative
§ retinal hypoxemia
- Treatment
o Intensive glycemic control
o Fenofibrates
o for proliferative retinopathy or mcular edema - laser
photocoagulation and.or anti-VEGF therapy
- It is the leading cause of CKD, ESRD and CKD renal
replacement therapy
- The pathogenesis of diabetic nephropathy is related to
chronic hyperglycemia -> soluble factors (growth factors,
AGE, endothelin), hemodynamic alterations in the renal
microcirculation, structural changes in the glomerulus
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 - Treatment o Orthostatic hypotension - adequate salt intake,
o Improved glycemic control avoidance of dehydration and diuretics, lower
o Control of BP extremities support hose and physical activity
o Protein intake of 0.8 mg/kg of body weight/day in
individuals with diabetic kidney disease GENITOURINARY AND GASTROINTESTINAL DYSFUNCTION
o referral to a nephrologist when albuminuria appears - GI symptoms:
and when the eGFRis <30ml/min/1.73m2 o Delayed gastric emptying, altered small and large
o Referral for transplant evaluation when GFR bowel motility
approaches 20 ml/min/1.73m2 - GU symptoms
o cystopathy, female sexual dysfunction
NEUROPATHY AND DM o erectile dysfunction and retrograde ejaculation
- It occurs in ~50% of individuals with long standing type 1 - Treatment - inadequate and non specific
and type 2DM o Small frequent meals that are easier to digest and low
- Additional risk factors are BMI and smoking, CVD, elevated in fat and fiber
triglycerides and hypertension o Avoid GLP-1 receptor agonist
- Distal symmetric polyneuropathy (DSPN) o Metoclopromide
o most common
o distal sensory loss and pain CARDIOVASCULAR DISEASE
o typically involves the lower extremities - CAD - PCI, CABG
o PE: sensory loss, loss of ankle DTR, abnormal position - Aggressive cardiovascular risk factor modifications
sense and muscular atrophy and foot drop - Use of Aspirin
o Annual screening 5 years after the diagnosis of Type - Cardiovascular Risk Factors
1DM and at the time of diagnosis for Type 2DM o Dyslipidemia
- Autonomic Neuropathy § Treatment Recommendation
o autonomic dysfunctions - cholinergic, adrenergic and § High intensity statin therapy
peptidergic systems § In patients 40-75 years with no risk factors:
o CV autonomic neuropathy - decreased heart rate moderate intensity statin therapy
variability, resting tachycardia, orthostatic § In patients <40 years old and additional risk
hypotension factors - moderate intensity statin therapy
o Gastroparesis and bladder emptying abnormalities o Hypertension
o sympathetic system dysfunction - hyperhidrosis of
upper extremities and anhidrosis of lower extremities LOWER EXTREMITY COMPLICATION
o hypoglycemia unawareness - Leading cause of nontraumatic lower extremity amputation
- Mononeuropathy in US
o less common - Pathogenic factors contributing to increase incidence of
o pain and motor weakness in the distribution of single lower extremity complication
nerve o neuropathy
o 3rd CN involvement - diplopia o abnormal foot biocmechanics
- Radiculopathy/Polyradiculopathy o PAD
o syndrome characterized by severe disabling pain in o poor wound healing
the distribution of one or more nerve roots - Risk factors
o accompanied by motor weakness o male sex
o self limited and resolve over 6-12 months o diabetes >10 years
- Treatment o peripheral neuropathy
o Prevention - good glycemic control o abnormal strucutre of foot
o lifestyle modification o PAD
o treatment of HPN, hypertriglyceridemia o smoking
o avoidance of alcohol, smoking o history of previous ulcer or amputation
o supplement with vitamins for possible deficiencies o visual impairment
o Duloxetine and Pregabalin o poor glycemic control
o Tapentadol o diabetic neuropathy
o Tricyclic antidepressants, gabapentine, venlafaxine, - The optimal therapy for foot ulcers and amputations is
carbamazepine, tramadol and topical capsaicin prevention through identification high risk patients,

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 education of patients and institution of measures to
prevent ulceration
- Patients with abnormal monofilament test - LOPS
- Screen for asymptomatic PAD for individuals >50 years old
- Interventions for diabetic foot ulcers or wounds
o off-loading
o debridement
o wound dressing
o appropriate use of antibiotics
o revascularization
o limited amputations

INFECTIONS
- Pneumonia, UTI, skin and soft tissue infections - more
- common in diabetic population
- Common organisms
o Pulmonary infections - gram negative organisms, S.
PHYSIOLOGIC RESPONSES TO DECREASING PLASMA GLUCOSE
aureus, M.tuberculosis
CONCENTRATION
o UTI - E. coli
- Underlying cause RESPONSE GLYCEMIC GLUCOSE
o abnormalities in CMI and phagocyte functions THRESHOLD COUNTERREGULATION
o diminished vascularization DECREASE 80-85 mg/dl Primary glucose
INSULIN regulatory factor/ first
DERMATOLOGIC MANIFESTATIONS defense against
- The most common skin manifestations of DM are xerosis hypoglycemia
and pruritus INCREASE 65-70 mg/dl Primary glucose
- Diabetic dermopathy or pigmented pretibial papules or GLUCAGON counter regulatory
diabetic skin spots - erythematous macule or papule factor/ second
- Necrobiosis lipoidica diabeticorum - uncommon, defense agains
predominantly in young woman that begins in pretibial hypoglycemia
region as erythematous plaque or papules that gradually INCREASE 65-70 mg/dl third defense against
enlarge, darkens and develops irregular margins with EPINEPHRINE hypoglycemia, critical
atrophic centers and central ulceration when glucagon is
- Acanthosis nigricans - hyperpigmented velvety plaques deficient
seen on the neck, axilla or extensor surfaces
- Lipoatrophy and lipohypertrophy - occurs in insulin INCREASE 65-70 mg/dl involved in defense
injection sites CORTISOL AND against prolonged
GROWTH hypoglycemia not
HYPOGLYCEMIA HORMONE critical
SYMPTOMS 50-55 mg/dl prompt behavioral
WHIPPLE’S TRIAD
defense against
- symptoms consistent of hypoglycemia
hypoglycemia (food
o Symptoms: Dizziness, hunger, tremor, palpitation,
ingestion
headache, cold-clammy perspiration, weakness
- low plasma glucose concentration measured with precise DECREASE <50 mg/dl compromised
method COGNITION behavioral defense
- relief of symptoms after the plasma glucose is raised against hypoglycemia
- Take note that insulin will start to decrease at a normal
level. 80-85 is still considered normal. That’s the time that
insulin is already going down
- When that is enough and the blood glucose goes to 65-70,
there will be increase in glucagon
- 65-70, cortisol and GH increases. But the effect is not as fast
because the effect of these two hormones take time.

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 - If walang sx, nakatulog na lang, do not force patient to eat.
Bring the patient to the ER because the patient might have
aspiration pneumonia or asphyxia.

CAUSES OF HYPOGLYCEMIA IN ADULTS

- Ill or medicated individual
o Drugs (insulin or insulin secretagogue, alcohol,
others)
o Critical Illness (Hepatic, renal or cardiac failure, sepsis,
inanition)
o Hormone deficiency (cortisol, glucagon, epinephrine)
o Non-islet cell tumor (Large mesenchymal tumor)
- Seemingly well individual
o Endogenous hyperinsulinism (Insulinoma, Functional
beta cell disorders, insulin autoimmune
hypoglycemia, insulin secretagogue)
- Accidental, surreptitious or malicious hypoglycemia

- Liver maintains blood glucose by inc hepatic glucose

output so if there is liver failure, there will be no glucose
- Renal failure – hindi nila ma-excrete ang insulin
- Cardiac failure – passive congestion that affects liver and
kidney
- Sepsis – inflamm conditions that can decrease stores of
glucose in the body
- Hormone deficiency – decrease in counter regulatory
hormones
- If you cannot see any other problem (liver, renal, heart
failure etc), one consideration is endogenous
hyperinsulinism
- These are the pxs who have a tumor in the pancreas that
causes elevation of insulin
- Treat by removing insulinoma
- Treat by eating if the px doesn’t want operation
- Accidental – nakalimutan na nakainom na ng gamot,
uminom ulit. Or 50 units na inject, dapat 5 units lang.

TREATMENT
- Urgent treatment: glucose tablets or glucose containing
food (20 g of glucose)
- IV glucose - if unable to eat
- IM glucagon
- Prevent recurrent hypoglycemia

- Treatment is FOOD
- URGENT: If awake, glucose tablets or glucose containing
food
- Prevent recurrent hypoglycaemia – esp in pxs with
insulinoma, they know if they’re about to get
hypoglycaemia. Diabetes – prevent recurrent hypogly by USE AT YOUR OWN RISK!
decreasing dose, revise food intake, revise medications if Notes from New Lecture PPT 2019, some recordings (Thank you
they have complications like renal problems or heart MS for the recordings part)
failure.

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