Diabetes mellitus

Diabetes mellitus
A modern epidemic
caused by
increasing obesity & reduced activity

Epidemiology
 Worldwide- 30 million patients in 1985, 177 million in 2000,
>360 million by 2030 (projected)- mostly in developing nations
 In US in 2008- 24 million with DM & 57 million with pre-diabetes
 Predicted lifetime risk of DM- 1 in 3 Americans born after 2000
 Prevalence ~7% in US (1 in 14)
 Prevalence increases with age-
 Age <20- 0.22%
 Age >20- 9.6%- ~1 in 10
 Age >60- 20.9%- ~1 in 5
 5th
leading cause of death, responsible for ~3 million deaths per
year

Insulin
 An anabolic peptide hormone
 Secreted by beta cells of pancreas
 Actions-
 Decrease liver glucose production
 Increase glycogen synthesis
 Promote glucose transport into muscle/fat (GLUT-4)
 Inhibit lipolysis, promote lipogenesis
 Inhibit protein catabolism, promote protein synthesis

Basic defect
Absolute deficiency of insulin
or insulin resistance with relative
insulin deficiency

Classification
 Type 1- immune-mediated/idiopathic- 5-10% of all
 Type 2- insulin resistance- 90-95% of all
 Gestational DM
 Other-
 Genetic defect of β-cell function- MODY1-6
 Genetic defect in insulin action- Type A insulin resistance
 Diseases of exocrine pancreas– pancreatitis, cystic fibrosis
 Endocrinopathies- acromegaly, Cushing’s, glucagonoma, pheochromo.
 Drug/chemical induced- steroids, β-blockers, thiazides
 Infections- congenital rubella, CMV
 Uncommon immune-mediated- anti-insulin receptor Abs., Stiff-man syn
 Other associated genetic syndromes- Down, Klinefelter, Turner,
Wolfram, Friedreich ataxia, Huntington chorea, Lawrence-Moon-Biedl

Pathogenesis
 Type 1- beta-cell destruction
 Genetic- identical twin concordance-30-70%, 3-4% risk if a
parent has DM, HLA-DR3/4 +ve
 Environmental- Coxsackie virus/rubella/mumps infection
 Autoimmunity- insulin/GAD/islet-cell antibodies
 Type 2- insulin resistance
 Genetic- identical twin concordance-70-90%,
40% probability of DM if both parents have DM
 Obesity- insulin resistance & relative insulin deficiency
 Insulin resistance- increased FFA & reduced adipokines
 Impaired insulin secretion- toxicity of increased glucose & FFA

Symptoms
 Polyuria, polydipsia, polyphagia
 Weight loss
 Impaired vision
 Increased infections
 DKA- rapid deep breathing (Kussmaul), nausea,
vomiting, abdominal pain, dehydration, altered
sensorium
 Macrosomia- baby >4 kg.
T1DM- mostly symptomatic
T2DM- mostly asymptomatic

Diagnosis
 FBG >126 mg%
 BG >200 mg% 2 hour after
75 gm oral glucose
 Symptoms of hyperglycemia
with RBG >200 mg%
 HbA1c >6.5% (proposed by ADA)

Pre-diabetes
Only inT2DM
FBG- 100-125- IFG
PPBG- 140-199- IGT

Screening
 High-risk only
 First degree relative with DM
 Previous IFG/IGT
 Obese- BMI >30
 Hypertension
 Hyperlipidemia
 Pregnancy or previous GDM or macrosomia
 On steroids
 h/o CAD/CVA, PCOD

Complications
 Acute-
 Diabetic ketoacidosis
 Hyperosmolar nonketotic coma
 Hypoglycemia
 Chronic-
 Microvascular- retino/nephro/neuro-pathy
 Macrovascular- dyslipidemia, hypertension,
vascular disease- CAD/CVA/PVD, diabetic foot

Management
Goals-
HbA1c- <6.5%
FBG- <100 mg%
PPBG- <140 mg%

Rx- T1DM
Insulin- basal long-acting analog with
bolus rapid-acting analog
Continuous subcutaneous insulin
infusion with an insulin pump

Insulin preparations
 Rapid-acting- aspart, lispro, glulisine
Onset- ~10 min., Peak- ~60 min., Effective x <5 hrs.
 Short-acting- regular
O- 30-60 min., P- 2-3 hrs., E x 5-8 hrs.
 Intermediate-acting- NPH
O- 2-4 hrs., P- 4-10 hrs., E x 10-16 hrs.
 Long-acting- glargine, detemir
O- ~6 hrs., No peak, E x upto 24 hrs.
 Premixed- 70/30, 50/50
No proven benefit of newer analogues over regular/NPH
insulin

Insulin prescription
 0.6 U/kg/day
 Subcutaneous injection
 Twice daily injection-
 Calculate total dose
 2/3rd
NPH, 1/3rd
regular
 2/3rd
in a.m., 1/3rd
in p.m.
 Multiple injections-
 Calculate total dose
 1/4th
NPH after dinner
 3/4th
regular- 40% BBF, 30% BL, 30% BD
Adjust, based on symptoms of hypoglycemia & blood glucose

Rx- T2DM
 Lifestyle modification- alcohol in moderation,
quit smoking
 Diet- practical
 Small frequent meals
 Whole grains, fruits, vegetables
 Low fat- <30% calories, low saturated fats
 High fibre
 Exercise- 30 mins./day x 5 days/week
 Weight loss- any is better than none
 Drugs
-

Drugs
 Biguanide- Metformin- reduces liver release of glucose
 Sulfonylureas- gli--- increase glucose stimulated insulin
secretion
 Thiazolidenediones- --glitazone- increase tissue insulin
sensitivity
 α-glucosidase inhibitors- Acarbose, Voglibose, Miglitol-
reduce glucose absorption
 Meglitinides- --glinide- stimulate insulin release
 Amylin analog- Pramlintide
 GLP analog (incretin mimetic)- Exenatide, Liraglutide
 DPP-4 inhibitors- --gliptin- increase incretin
 Insulin & its analogs

Practical drug use
 Dx of Type 2 DM
 Lifestyle changes
 +Metformin
 +sulfonylurea or glitazone or gliptin
 +glitazone or gliptin or sulfonylurea
 +NPH Insulin once/twice a day
 +regular Insulin before each meal

Monitoring glucose control
 HbA1c- every 3 months
 Self-monitoring of blood glucose-
ideal, but impractical, specially in T2DM
 Random/planned checking of FBG/PPBG
 Beware of HYPOGLYCEMIA

T1DM T2DM
 Onset <30 years
 Obesity uncommon
 Very low Insulin level
 Twin concordance:
<50%
 Asso. With HLA-D Ags.
 Autoantibodies +nt
 Mostly symptomatic
 Rx- Insulin
 Onset >30 years
 Obesity common
 Insulin- variable
 Twin concordance:
>90%
 No HLA association
 No autoantibodies
 Mostly asymptomatic
 Rx- OHAInsulin

Management of prediabetes
Modest weight loss- 5-7%
Regular physical activity
(30 mins x 5 days/week)
Drugs- metformin, acarbose, rosiglitazone

Syndrome X
 Metabolic-
 IFG- >100 mg%
 Central obesity- WC-
>102/90-M, >88/80-F
 HT- >130/85 mm Hg
 TG- >150 mg%
 HDL-C- <40-M, <50-F
 Prevalence ~20-33%
 Increases R/O CVD
 Cardiac-
 Angina
 Abnormal stress test
 Normal cor. Angiogram
 More in females
 Commonly associated
with metabolic
Syndrome X

Diabetes and pregnancy
 Good glycemic control (target HbA1c <6.1%),
before conception and during pregnancy
 HbA1c >10%- avoid pregnancy
 Monitor weight gain and blood pressure
 SMBG
 Safe anti-diabetics-
Insulin, Metformin, Glibenclamide
 Stop ACEI, statins, other anti-diabetics
 Check for retinopathy and nephropathy

Gestational DM
 OGTT at 24-28 weeks
 Diagnostic criteria- 75 gm. oral glucose
 Fasting- >95 mg%
 1 hour post-glucose- >180 mg%
 2 hour post-glucose- >155 mg%
 Risk factors- OGTT at 16-18 weeks
 Age >25 years
 BMI >25
 F/H of DM
 h/o IFG/IGT, PCOD, bad obstretic history, previous GDM,
delivery of baby >4 kgs

Management of GDM
 Diet
 Exercise
 SMBG
 Target- FBG- 60-100, 1-hr PPBG-<140
 Avoid hypoglycemia
 Ultrasound at 18-20 weeks for congenital
malformation
 US every 4 weeks from 28th
-36th
week for fetal
growth and amniotic fluid volume
 Delivery after 38 weeks (normal/LSCS)

Complications of DM
Acute
or
Chronic

Hypoglycemia
 A complication of treatment of DM with Insulin & its
secretagogues- sulfonylureas/meglitinides
 Symptoms- appear with BG <60 mg%
 Anxiety, paresthesia, palpitation
 Confusion, headache, blurred/double vision, seizures, coma
 Dx-
 Blood glucose correlating with clinical findings
 Response to glucose/dextrose administration
 Serum insulin/C-peptide levels
 Rx-
 Oral sugar or IV dextrose
 Parenteral glucagon

Diabetic ketoacidosis
 Acute complication, mostly of T1DM
 Mortality- 5-10%
 Absolute insulin deficiency or relative insulin
deficiency due to stress/drugs
 Insulin decreased, glucagon/epinephrine
increased
 Hyperglycemia, mobilization of fat & protein for
gluconeogenesis, increased FFA, accelerated ketogenesis
 Characterized by hyperglycemia,
hyperketonemia, metabolic acidosis

DKA- clinical
 Nausea, vomiting, abdominal pain,
polyuria, dehydration (hypotension,
decreased UO), altered sensorium
 Dx- hyperglycemia, high anion-gap
metabolic acidosis, ketones in urine
 Associated hyponatremia,
hyperkalemia, elevated BUN/creatinine
 Look for precipitating illness/drug

DKA- management
 IV fluids- average fluid deficit is 4-5 liters
 NS- raise BP, ensure adequate urine output
 ½ NS- normal BP, adequate UO
 DNS- BG ~250 mg%
 IV Insulin
 0.1 U/kg bolus, followed by
 0.1 U/kg/hour infusion continued till anion gap normalizes & no
ketones in blood/urine
 Manage potassium
 Initial hyperkalemia due to acidosisextracellular shift
 Correction of acidosis & Insulin shift K in to cells
 Monitor & replace K frequently

Hyperosmolar coma
 Acute complication, mostly of T2DM
 Mortality- ~50%
 Characterised by hyperglycemia, dehydration,
hyperosmolar plasma, altered sensorium
 No ketosis, because Insulin present prevents
ketogenesis
 Dx- hyperglycemia, increased serum
osmolarity
 With raised BUN/Cr, hypo/hyper-natremia,
normal/mildly low K, mild lactic acidosis

Hyperosmolar coma- Rx
 IV fluids- average deficit ~10 liters
 NS- raise BP, adequate urine output
 ½ NS- when BP normalizes
 IV Insulin
 0.1 U/kg IV bolus, then
 0.1 U/kg/hr infusion till BG~200 mg%, then
 1-2 U/hr infusion till complete rehydration
 Correction of hypokalemia
 40 mEq/hr for K<3.3 mEq/L, then
 20-30 mEq/hr for K 3.3-5.0 mEq/L

Hypertension
 ~25% of T1DM & ~50% of T2DM
patients have HT
 HT accelerates chronic complications of
diabetes
 Target BP- 130/80 mm Hg in diabetics
 Preferable anti-HTive- ACEI/ARB
 Individualize HT Rx according to
comorbidities

Lipid management
 Dyslipidemia worsens cardiovascular
complications of DM
 Goals- LDL- <70, HDL- M>40; F>50, TG
<150
 Lifestyle modifications- diet, exercise,
smoking
 Statins are Rx of choice
 Fibrates (fenofibrate) for raised TG
 Niacin/nicotinic acid for low HDL
 Aspirin for primary prophylaxis of CAD

Microvascular complications
Annual examination
T1DM- 5 years after Dx
T2DM- at the time of Dx

Diabetic retinopathy
 Nonproliferative
Microaneurysms, hard exudates, occ. soft exudate/h’age
 Preproliferative
Venous beading, multiple cotton wool spots & retinal h’age
 Proliferative
New vessels on disc/elsewhere , preretinal/vitreous h’age
 Macular edema
 Cataract
 Glaucoma

Diabetic retinopathy
 A major cause of blindness
 Over lifetime 70% of IDDM will develop
PDR & 40% will have macular edema
 Mostly asymptomatic
 Regular monitoring required for timely
detection
 Rx- LASER
 Prevention- good glycemic control

Diabetic nephropathy
 Leading cause of ESRD
 AlbuminuriaHTCRIESRD
 40% of IDDM have ESRD after 20 yrs.
 Earliest finding of microalbuminuria-
30-300 mg albumin
excretion/24hours
 Pathology- glomerulosclerosis-
thickened GBM & mesangial expansion

Diabetic nephropathy
 Prevention-
 Monitoring & control of BS & BP
 Prompt Rx of UTI
 Avoid potentially nephrotoxic drugs/dyes
 Rx-
 Aggressively monitor & treat BP- target <130/80
 Limit dietary protein intake- <0.8 mg/kg/day
 Good glycemic control- using Insulin
 Rx other urinary problems
 Early RRT- dialysis/transplantation

Diabetic neuropathy
 ~12% at Dx & ~60% after 25 years
 Types-
 Distal symmetrical sensory polyneuropathy-
causes neuropathic ulcers and arthropathy
 Focal neuropathy- ischemic, sudden-onset
asymmetrical, sensorimotor, self-limited
 Autonomic neuropathy- gastroparesis,
diarrhea/constipation, orthostatic
hypotension, bladder dysfunction, impotence

Diabetic neuropathy
 Monitor for s/s
 Good glycemic control
 Foot care- avoid trauma, good footwear
 Painful neuropathy- amitriptyline,
carbamazepine, gabapentin, pregabalin
 Other problems- symptomatic treatment

Cardiovascular disease
 Leading cause of morbidity & mortality in
diabetics
 Risk 2-3 times greater in diabetics
 Risk equal in women with diabetes
 Risk factors-
 Poorly controlled DM
 Smoking
 HT
 Hyperlipidemia

CVD in diabetes-
management
Lifestyle- diet & exercise
Monitor for early s/s
Aggressively control risk factors

Foot problems in diabetics
 DM is leading cause of amputation
 Due to peripheral neuropathy, PVD &
increased infections
 Needs-
 Good glycemic control
 Quit smoking
 Early detection of neuropathy
 Proper footcare & footwear
 Correct deformities, other surgeries as required

Diabetes mellitus

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