This document provides an overview of type 2 diabetes mellitus (DM), including its pathophysiology, risk factors, clinical presentation, screening and diagnosis, management, and treatment. It discusses DM as characterized by hyperglycemia, insulin resistance, and relative insulin deficiency. Risk factors include genetic susceptibility and environmental exposures. Symptoms result from hyperglycemia and long-term complications can include damage to blood vessels and nerves. Treatment involves lifestyle modifications, glucose monitoring, glycemic control through pharmacotherapy including various oral medications and insulin, and management of cardiovascular risk factors.

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14th Nov

2. DIABETES MELLITUS (II)

3. DIABETES MELLITUS (DM)
Types
• DM-I
• DM-II
• Gestational DM
• Others (monogenic diabetic syndrome,
pancreatitis,…)
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4. • Type 2 diabetes mellitus is characterized by :
 Hyperglycemia,
 Insulin resistance, and
 Relative impairment in insulin secretion
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5. Fig. no. 1 Glucose homeostasis
Source: Robbins and Cotrans, basis of pathology,9e
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6. Fig. No. 2 Mechanism of glucose-stimulated insulin secretion
Source: Harrison’s,19e
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7. Fig. no. 3 Metabolic effect of insulin
Source: Robbins and Cotrans, Basis of pathology,9E
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8. • Pathology
(Genetic Susceptibility, Environmental factors, metabolic defects)
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9. RISK FACTORS
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10. 1. GENETIC SUSCEPTIBILITY
• A complex interaction among many genes and environmental factors
• >100 genetic loci impacting risk of type 2 diabetes
• The lifetime risk for a first-degree relative of a DM-II patient = 5 to 10 times
• At least one parent with the disease in 39 % DM-II Pt.
First-degree relatives of patients with type 2 diabetes frequently have impaired
nonoxidative glucose metabolism (indicative of insulin resistance) long before they
develop type 2 diabetes
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11. • Even among groups with increased genetic risk for diabetes, however,
environmental factors play a major role in the development of diabetes.
As an example, the prevalence of diabetes among Pima Indians in Mexico
less than one-fifth that in United States Pima Indians (6.9 versus 38
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12. 1. Pancreatic development and B-cell Function
• Diabetic susceptible loci - involved in pancreatic development and
insulin synthesis (SLC30A8, HHEX/IDE, and KCNJ11)
2. MODY2 and MODY4 — Maturity onset diabetes of the young
(MODY) - a rare cause of type 2 diabetes that has autosomal
dominant transmission and features of both impaired insulin
and insulin resistance
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13. ENVIRONMENTAL EXPOSURE
• Chronic exposure to inorganic Arsenic in drinking water
• Exposure to bisphenol A ( found in plastic)
• Chronic exposure to Organophosphate and Chlorinated
pesticides
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14. METABOLIC DEFECTS
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15. Fig. No. 5 Metabolic changes during DM II Development
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18. CLINICAL FEATURES
Symptoms of Hyperglycemia
Polydipsia, dry mouth
Polyphagia
Polyuria
Weight loss
Nocturia
Tiredness, nausea and headache
Blurring of vision
Genital candidiasis
Mood change, irritability
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19. Fig no.6. Clinical manifestation due to metabolic derangement
Source : Basis of pathology ,9e
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20. •Complications
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21. Fig no. 7. Clinical manifestation due to metabolic derangement
Source: Basis of pathology,9e
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23. Fig. No. 8 Retinopathy and DM relation
source: Harrison’s,19e
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24. SCREENING TESTS
Tests includes:
• Fasting plasma glucose
• Glycated hemoglobin
• 2H- plasma glucose during OGTT
( Due to inconvenience not used commonly for screening except
in pregnancy)
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25. Normal
• Fasting Plasma Glucose : <100 mg/dL (5.6 mmol/L)
(no calorie intake in last 8 hours)
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26. INCREASED RISK FOR DM (PRE-DIABETES )
• Impaired fasting Glucose (IFG) – 100-125 mg/dL
• Impaired glucose tolerance (IGT) – 140 -199 mg/ dL (2h plasma glucose,
75 g)
• Hemoglobin A1C- 5.7 – 6.4 %
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27. DM DIAGNOSIS
• Fasting Plasma Glucose (IFG) – >=126 mg/dL
• Hemoglobin A1C- >=6.5 %
• 2H plasma glucose - >= 200 mg/dL during OGTT
• Random Plasma glucose >= 200 mg/dL
Source : ADA, 2019
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28. •Management
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29. TREATMENT APPROACH
• Education,
• Evaluation for micro- and macrovascular complications,
• Attempts to achieve near Normoglycemia,
• Minimization of cardiovascular and other long-term risk
factors, and
• Avoidance of drugs that can exacerbate abnormalities of
insulin or lipid metabolism
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30. TREATMENT GOALS
Index Goal
Glycemic control
A1C <7.0%
Preprandial capillary plasma glucose 4.4–7.2 mmol/L (80–130 mg/dL)
Peak postprandial capillary plasma
glucose (90-180 min)
<10.0 mmol/L (<180 mg/dL)
Blood pressure <130/80 mm of Hg
Lipids
Low-density lipoprotein <2.6 mmol/L (100 mg/dL)
High-density lipoprotein >1 mmol/L (40 mg/dL) in men
>1.3 mmol/L (50 mg/dL) in women
Triglycerides <1.7 mmol/L (150 mg/dL)
Source : ADA,
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32. DIABETES EDUCATION
• Self-monitoring of blood glucose
• Insulin administration
• Prevention and management of hypoglycemia
• Foot and skin care
• Diabetes management before, during, and after exercise
• Risk factor–modifying activities
Stop alcohol and smoking. Alcohol can precipitate or protract
hypoglycemia by suppressing gluconeogenesis. 32

33. NUTRITION
• Low-calories diet that is low-fat or low-carbohydrate
• Minimal trans fat consumption
• Monitor carbohydrate intake in regards to calories
• Sucrose-containing foods may be consumed with adjustments
in insulin dose
• Non-nutrient sweeteners
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34. EXERCISE
• Exercise  Cardiovascular risk reduction, reduced blood pressure, maintenance
of muscle mass, reduction in body fat, and weight loss, increased insulin
sensitivity.
• 150 min/week (distributed over at least 3 days) of moderate aerobic physical
activity.
• Exercise-related hypoglycemia though uncommon can occur in individuals
taking either insulin or insulin secretagogues.
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35. MONITORING GLYCEMIC CONTROL
• Plasma glucose measurements by the patient (self blood glucose
monitoring)
• Assessment of long-term control by the physician (HbA1c)
• Permits the patient to make adjustment in insulin treatment
• Ketoacidosis may be avoided
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37. PHARMACOLOGICAL THERAPY
• Initial therapy
Begin with lifestyle changes
If glycemic goals not achieved metformin monotherapy added
• Combination therapy
If A1C target not achieved after approx 3 months,
Metformin and one of 6 treatment option(sulfonylurea, thiazolidinedione,
DPP4 inhibitor, SGLT2 inhibitors, GLP1 receptor agonists, or basal insulin)
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38. CONTINUE...
• Insulin therapy eventually
Basal insulin alone : most convenient initially
But if A1C remains above target, advance to combination injectable
therapy
• Bariatric surgery in BMI>35kg/m2 if lifestyle and pharmacological
therapies can’t control diabetes or comorbidities
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40. WHEN TO START
INITIAL PHARMACOLOGICAL THERAPY
• A1C - >7.5 to 8 % pharmacologic therapy with lifestyle modification
(However, for those patients who have clear and modifiable contributors to
hyperglycemia and who are motivated to change them (eg, commitment to reduce
consumption of sugar-sweetened beverages), a three-month trial of lifestyle
modification prior to initiation of pharmacologic therapy is warranted)
• For highly motivated patients with A1C near target (ie, <7.5 percent), a three- to
six-month trial of lifestyle modification before initiating pharmacologic therapy is
reasonable.
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42. ANTI-HYPERGLYCEMIC THERAPY
1. A1C < 9%
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43. 3. A1C >= 9%
3 A1C. >= 10 %
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45. INSULIN DOSING REGIMENS
• Choice of regimen depends on desired degree of glycemic control
• Most require two or more injection of insulin daily
• Combination of short acting and intermediate acting insulin is given
usually soluble and isophane insulin
• Available combination is 30:70 and 50:50 (soluble and isophane
insulin)
• Twice daily dosing (2/3rd dose - morning before breakfast and 1/3rd
dose – after dinner) 45

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47. SIDE EFFECTS OF INSULIN THERAPY
• Hypoglycemia
• Weight gain
• Peripheral edema
• Insulin antibodies(animal insulin)
• Local allergy(Rare)
• Lipodystrophy at injection site
Insulin treatment causes salt and water retention in short
treatment 47

48. AMYLIN AGONIST
• MOA
Causes slow gastric emptying and decreases glucagon secretion
Increases satiety, weight decrease
Reduces postprandial glycemia
• ADR- nausea, vomiting and increases risk of hypoglycemia with insulin
• Example- Pramlinitide
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49. HYPEROSMOLAR HYPERGLYCEMIC STATE (HHS)
Cause : Relative insulin deficiency and inadequate fluid intake
Diagnostic criteria :
• Serum glucose : >600 mg/dL
• Arterial pH >7.3
• Serum bicarbonate > 15 mEq/L
• And minimal ketonuria and ketonemia
# Neurologic abnormalities : Mental confusion, lethargy, coma(25-50% cases)
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50. Source : UptoDate
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51. GUIDELINE FOR ONGOING DM
• Optimal and individualized glycemic control
• Self-monitoring of blood glucose (individualized
frequency)
• HbA1C testing (2-4 times/year)
• Patient education in DM management (annual)
• Medical nutrition therapy and education
• Eye examination (annual or biannual )
• Foot examination (1-2 times/year, daily by patient)
• Screening for diabetic nephropathy (annual)
• Blood pressure measurement (quarterly)
• Lipid profile and serum creatinine (annual)
• Influenza/pneumococcal/hepatitis B immunization
Source : Harrison’s, 19E
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52. REFERENCES
1. American Diabetic Association, ‘Standards of Medical Care in
Diabetics’,2019
2. Alvin C. Powers, ‘Diabetes Melitus:Diagnosis, Classification and
Pathophysiology’, Harrison’s Principle of Internal Medicine, 19th
edition
3. Robbin’s and cotrans, Basisis of pathology, 9E
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53. Thank you
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