Contents

Type 2 Diabetes Mellitus — Exam Notes 1

Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Classification of Type 2 DM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Diagnosis (WHO/ADA criteria) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
HbA1c and Fructosamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1. Lifestyle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Oral Hypoglycemic Agents (OHAs) — mainstay of Type 2 DM treatment . . . 2
3. Insulin therapy in Type 2 DM . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Acute Complications Relevant to Type 2 DM . . . . . . . . . . . . . . . . . . . . . . 3
Hyperosmolar Hyperglycemic State (HHS) — classically a Type 2 DM emergency 3
Hypoglycemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Chronic Complications of Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Type 2 Diabetes Mellitus — Exam Notes

(Compiled from Archit Boloor’s “Exam Preparatory Manual for Undergraduates—Medicine”
+ standard references)

Definition
Diabetes mellitus (DM) is the most common endocrine disease — a metabolic disorder
characterized by hyperglycemia due to insulin deficiency, insulin resistance, or both.

Classification of Type 2 DM
A heterogeneous condition characterized by: - Insulin resistance — body’s cells don’t re-
spond properly to insulin. - Impaired insulin secretion — pancreas doesn’t release enough
insulin. - Increased hepatic glucose production — liver releases too much glucose.
Usually preceded by a “pre-diabetes” phase, classified as: - Impaired Fasting Glucose
(IFG), or - Impaired Glucose Tolerance (IGT)
(Note: Type 2 DM is distinct from Type 1 DM, which involves absolute insulin deficiency from
autoimmune β-cell destruction — HLA genes, insulitis, autoantibodies, “honeymoon phase”
are Type 1-specific concepts and not part of Type 2 pathophysiology.)

Diagnosis (WHO/ADA criteria)

Euglycemic (Normal) Pre-diabetes Diabetes

Fasting glucose <100 mg/dL 100–125 mg/dL (IFG) ≥126 mg/dL
2-hr OGTT (75g) <140 mg/dL 140–199 mg/dL (IGT) ≥200 mg/dL

WHO diagnostic criteria (Box 3.1): - Fasting plasma glucose >126 mg/dL (7.0 mmol/L),
OR - Random plasma glucose >200 mg/dL (11.1 mmol/L) with classical symptoms, OR - One

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abnormal value is diagnostic if symptomatic; two values needed if asymptomatic. - HbA1c
>6.5% (48 mmol/mol) is diagnostic on its own.
Pre-diabetes: HbA1c 5.7–6.4%. Associated with metabolic syndrome; risk of progression
to frank diabetes & CVD. Weight loss (5–10%) + exercise recommended; no drug therapy
routinely recommended (though metformin/acarbose have been tried).

Clinical Features
• Classical triad: polyuria, polydipsia, polyphagia (with weight loss despite polypha-
gia).
• Immune dysfunction: recurrent TB, non-healing wounds, candidal vulvitis/balanitis, re-
current styes, UTIs.
• End-organ presentations at diagnosis: retinopathy, nephropathy, neuropathy (Type 2 DM
often has a long silent period before diagnosis, so these may already be present).
• Risk factors: obesity, pregnancy, family history of diabetes.

HbA1c and Fructosamine

• HbA1c: reflects glycemic control over preceding 3 months (RBC lifespan). Target
<7%. Falsely low in ↑RBC turnover (hemolytic anemia); falsely high with ↓turnover
(aplastic anemia).
• Fructosamine (glycated albumin): reflects control over preceding 2–3 weeks; useful
in anemia/hemoglobinopathy/pregnancy.

Management
1. Lifestyle
Medical nutrition therapy + exercise — first-line, especially in pre-diabetes/early Type 2 DM.

2. Oral Hypoglycemic Agents (OHAs) — mainstay of Type 2 DM treatment

Key adverse
Class MOA Examples HbA1c ↓ effect
Biguanide ↓hepatic Metformin 1–2% GI upset; C/I in
gluconeogenesis re-
nal/hepatic/cardiac
failure, hypoxia
(lactic acidosis
risk); does NOT
cause
hypoglycemia
Sulfonylureas Close K-ATP Glimepiride, 1–2% Hypoglycemia,
channel → glipizide, weight gain
insulin secretion gliclazide
α-Glucosidase ↓GI glucose Acarbose, 0.5–0.8% Flatulence
inhibitors absorption miglitol
Thiazolidinediones ↓insulin Pioglitazone, 0.5–1.4% Edema, CHF,
resistance rosiglitazone fractures,
bladder cancer
risk
(pioglitazone)

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 Key adverse
Class MOA Examples HbA1c ↓ effect
SGLT2 ↓renal glucose Canagliflozin, 0.4–1.1% Genital/urinary
inhibitors reabsorption dapagliflozin, infections; no
empagliflozin hypoglycemia;
weight loss
GLP-1 agonists ↑insulin, Exenatide, 0.5–1.0% Nausea,
(injectable) ↓glucagon, slow liraglutide pancreatitis risk
gastric
emptying
Amylin agonist Slows gastric Pramlintide 0.25–0.5% Nausea
emptying,
↓glucagon
Bile acid Unknown Colesevelam 0.5% GI upset
sequestrant glucose
mechanism

Metformin contraindications: malabsorption/GI intolerance, BMI <21 with weight loss,

organ failure (creatinine >1.4, hepatic/cardiac failure), active B12 deficiency.

3. Insulin therapy in Type 2 DM

Indicated when: - Uncontrolled on maximal OHA therapy - During pregnancy - During acute
illness/surgery - During hyperglycemic emergencies (see below)

Acute Complications Relevant to Type 2 DM

Hyperosmolar Hyperglycemic State (HHS) — classically a Type 2 DM emergency
• Seen typically in elderly Type 2 DM patients.
• Marked hyperglycemia (>600 mg/dL), high serum osmolality (>320 mOsm/kg), mini-
mal/no ketosis (unlike DKA), profound dehydration, altered sensorium/coma.
Diagnostic criteria comparison (Table 3.19):

Feature HHS
Plasma glucose >600 mg/dL
Arterial pH >7.30
Serum bicarbonate >15 mEq/L
Anion gap <12 mEq/L
Mental status Stupor/coma
Ketones Negative to trace

Management: aggressive IV fluid replacement (larger deficit than DKA), IV insulin infusion,
careful electrolyte (especially potassium) correction, treat the precipitating cause.
(Note: DKA is possible but rare in Type 2 DM — it is predominantly a Type 1 DM emergency,
so it is not covered in detail here.)

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Hypoglycemia
• Causes: insulin or sulfonylurea excess, missed meals, exercise, renal failure (↓insulin
clearance).
• Symptoms: autonomic (sweating, tremor, palpitation, hunger) and neuroglycopenic (con-
fusion, seizure, coma).
• Treatment: oral glucose if conscious; IV dextrose (25–50 mL of 50% dextrose) or IM
glucagon if unconscious.

Chronic Complications of Diabetes

(Apply to both types, but Type 2 DM patients often already have complications at the time of
diagnosis, due to a long preceding asymptomatic period.)
A. Vascular - Microvascular: - Ophthalmic: diabetic retinopathy (non-proliferative & pro-
liferative), cataract, glaucoma. - Neuropathy: sensory, motor, sensorimotor, autonomic. -
Nephropathy: microalbuminuria → macroalbuminuria → chronic kidney disease. - Diabetic
foot disease. - Macrovascular: coronary artery disease, peripheral vascular disease, cere-
brovascular disease.
B. Nonvascular: gastroparesis, infections, skin changes, hearing loss.

Metabolic Syndrome
Cluster of central obesity + insulin resistance + dyslipidemia + hypertension — very
closely tied to the pathogenesis of Type 2 DM and significantly increases cardiovascular risk.