Approach to Diabetes

Mellitus
Lt Col Kumar Roka
MD
Dept of Medicine
Army Hospital / NAIHS
Definition
Group of common metabolic disorder that
share the phenotype of hyperglycemia
Criteria
Symptoms of
diabetes(polyuria ,polydipsia, weight loss)
+ RBG ≥ 200 mg/dl
OR
Fasting blood glucose(no caloric intake for
8 hours) ≥ 126 mg/dl
OR
2 hour plasma glucose ≥ 200 mg/dl during
an oral GTT
Criteria
Impaired fasting glucose
FPG = 100 – 125 mg/dl
Impaired glucose tolerance
On oral GTT plasma glucose level between 140
and 199 mg/dl.

Recently designated as prediabetes

25-40% risk of developing type 2 DM over 5
years
Etiologic classification
Type 1 DM
A. Immune mediated
B. Idiopathic
 Type 2 DM
 Genetic defect of ß cell function
characterized by mutations ( MODY 1-6 ,
mitochondrial DNA, proinsulin or insulin
conversion , subunit of ATP sensitive K
channel)
Etiologic classification
Other
Genetic defect in insulin action
Type A insulin resistance
Leprechaunism
Rabson – Mendenhall syndrome
Lipodystrophy syndrome
Etiologic classification
Disease of exocrine pancreas
 pancreatitis, pancreatectomy , neoplasia, cystic
fibrosis, fibrocalculous pancreatopathy
Endocrinopathy
 Acromegaly, Cushing’s syndrome, Glucagonoma,
Pheochromocytoma ,Hyperthyroidism,
Somatostatinoma
Drug or chemical induced
Pentamidine, nicotinic acid, steroids, thyroid
hormone,
Thiazides ,phenytoin , protease inhibitor , clozapine
Etiologic classification
Infections
Congenital rubella, CMV ,coxsackie
Uncommon form of immune mediated
diabetes
Stiff person syndrome, anti insulin receptor
antibodies
Other genetic syndrome
Down’s syndrome, Turner’s syndrome,
Klinefelter’s syndrome, Friedrich’s ataxia,
huntingtons chorea
Clinical evaluation
History
Weight
Family history of DM & its complication
Risk factors for CVS disease
Exercise
Smoking
Ethanol use
Clinical evaluation
History
Symptoms of hyperglycemia
 Polyuria, polydipsia
 Weight loss
 Fatigue
 Weakness
 Blurry vision
 Frequent superficial infection ( vaginitis , fungal

skin infection)
 Slow healing of skin lesions after minor trauma
Clinical evaluation
Examination
Weight or BMI
Orthostatic blood pressure
Peripherral pulses
Foot examination(peripheral neuropathy,
calluses, superficial fungal infections, nail
diseases, ankle reflexes, foot deformities )
Retinal examination
Insulin injection sites
Teeth & gum examination for periodontal
disease
Laboratory evaluation
A1C
 Fasting lipid profile, including total LDL and
HDL cholesterol and triglycerides
 Liver function tests
 Test for microalbuminuria
 Serum creatinine and calculated GFR
 Thyroid-stimulating hormone
 Screen for celiac disease in type 1 diabetes
and as indicated in type 2 diabetes
Criteria for testing for diabetes in asymptomatic
adult individuals

1. Considered in all individuals at age 45

years and above, particularly in those with
a BMI 25 kg/m2*, and, if normal, should
be repeated at 3-year intervals.
Criteria for testing for diabetes in asymptomatic
adult individuals
2) Considered at a younger age or be carried
out more frequently in individuals who are
overweight (BMI 25 kg/m2*) and have
additional risk factors:
 Habitually physically inactive
 First-degree relative with diabetes
 High-risk ethnic population (e.g., African
American, Latino, Native American, Asian
American, Pacific Islander)
 Delivered a baby weighing 9 lb or had GDM
Criteria for testing for diabetes in asymptomatic
adult individuals
 Hypertensive (140/90 mmHg)
 HDL cholesterol level 35 mg/dl (0.90
mmol/l) and/or a triglyceride level 250
mg/dl (2.82 mmol/l)
 PCOS
 On previous testing, had IGT or IFG
conditions associated with insulin
resistance (e.g., PCOS or acanthosis
nigricans)
 History of vascular disease
Testing for type 2 diabetes in children

 Overweight (BMI 85th percentile for age

and sex, weight for height 85th percentile,
or weight 120% of ideal for height)
Plus any two of the following risk factors:
 Family history of type 2 diabetes in first
or second-degree relative
 Race/ethnicity (Native American, African
American, Latino, Asian American, Pacific
Islander)
Testing for type 2 diabetes in children

Signs of insulin resistance or conditions

associated with insulin resistance (acanthosis
nigricans, hypertension, dyslipidemia, or
PCOS)
 Maternal history of diabetes or GDM

Age of initiation: age 10 years or at onset of

puberty, if puberty occurs at a younger age
Frequency: every 2 years
Test: FPG preferred
Gestational DM
High risk women should be tested for GDM
as early as possible with FPG or RBG
High-risk women not found to have GDM at
the initial screening and average-risk women
should be tested between 24 and 28 weeks of
gestation with OGTT ( 100 gm)
Gestational DM
High risk cases
Marked obesity,
 Personal history of GDM
 Delivery of a previous large-for gestation-age
infant
 Glycosuria
 Polycystic ovary syndrome
 Strong family history of diabetes
Gestational DM
Diagnostic criteria for the 100-g OGTT
Fasting : 95 mg/dl,
1 h : 180 mg/dl
2 h :155 mg/dl
 3 h :140 mg/dl.
Two or more of the plasma glucose values
must be met or exceeded for a positive
diagnosis for GDM
Management
Goals
Eliminate symptoms related to hyperglycemia
Reduce or eliminate long term complications
Allow patient to achieve normal lifestyle
Treatment goals
Glycemic control
A1C < 7.0%*
Preprandial capillary PG 90–130 mg/dl
Peak postprandial capillary PG <180 mg/dl
Blood pressure 130/80 mmHg
Lipids
LDL 100 mg/dl
Triglycerides 150 mg/dl
HDL 40 mg/dl
Education
Diabetes education
Self monitoring of blood glucose
Urine ketone monitoring ( Type 1 DM)
Insulin administration
Management during illness
Management of hypoglycemia
Foot and skin care
Management before, during and after exercise
Risk factor modifying activities
Medical nutrition therapy
Fat
20-35% of total caloric intake
Saturated fat < 7 % of total calories
< 200 mg/day of dietary cholesterol
Two or more serving of fish per week
Minimal trans fat consumption
Medical nutrition therapy
Carbohydrate
45-65% of total caloric intake ( low
carbohydrate diets not recommended)
Amount & type of carbohydrate important
( Glycemic index)
Sucrose containing food may be consumed
with adjustment in insulin dose
Medical nutrition therapy
Proteins
10-35% of total calorie intake ( high protein
diet not recommended)
Other component
Fiber containing food
Nonnutrient sweeteners
Exercise
150 min/week of moderate-intensity
aerobic physical activity(50–70% MHR) or
90 min/week of vigorous aerobic exercise
(70% MHR)
3 days/week , ( no more than two 2
consecutive days without physical
activity).
In the absence of contraindications,
Resistance exercise 3/week, targeting all
major muscle groups, 3 sets of 8 –10
repetitions at a weight that cannot be
lifted more than 8–10 times. ( Type 2 DM)
Glycemic control
Type 1 DM
Glycemic control
Insulin
0.5-1.0U/kg /day in divided doses with 50% as
basal insulin
Short acting insulin analogues should be
injected just before ( <20min) and plain insulin
30-45 min prior to meals
Inhaled insulin is short acting, used for
prandial coverage
1-3mg blisters equivalent to 3&8 U of injected
regular insulin respectively
 Insulin
Preparation Time of action(h)
Onset Peak Duration

Short acting SC

Lispro <0.25 0.5-1.5 3-4

Aspart <0.25 0.5-1.5 3-4

Glulisine <0.25 0.5-1.5 3-4

Regular 0.5-1.0 2-3 4-6

Inhaled regular <0.25 0.5-1.5 4-6

Long acting

NPH 1-4 6-10 10-16

Detemir 1-4 - 12-20

Glargine 1-4 - 24
 Insulin
Preparation Time of action(h)
Onset Peak duration
Insulin combination
75/25- 75%protamine lispro, <0.25 1.5 Upto10-16
25% lispro

70/30- 70%protamine aspart, <0.25 1.5 Upto10-16

30% aspart

50/50- 50%protamine lispro, <0.25 1.5 Upto10-16

50% lispro

70/30- 70% NPH, 30% 0.5-1 Dual 10-16

regular insulin

50/50- 50%NPH , 50% 0.5-1 Dual 10-16

regular insulin

Dual : two peaks , one at 2-3 h , second several hours later

Multiple injection
Mixtard
Continuous infusion
Glycemic control
Other agents
Pramlintide ( analogue of amylin)
15µg SC before each meal ( Max- 30-60 µg )
Reduce post prandial glycemic excursions
Reduces A1c by 0.25-0.5%
α-glucosidase inhibitor
Acarbose (50-100mg )
Miglitol ( 50 mg)
Glycemic control
Type 2 DM
OHA
Insulin secretagogues
Interact with ATP sensitive K channel on β cells
Best in recent onset DM ( < 5 years)
A1c reduction 1-2%
Reduces both fasting and PP glucose
Main side effect is hypoglycemia
Avoided in renal & hepatic dysfunction
Sulfonylurea's have drug interaction with
warfarin , aspirin, ketoconazole & fluconazole
 Insulin secretagogues
Generic name Approved dosages Duration of action
(mg/d) ( h)
Sulfonylurea – first gen
Chlorpropamide 100- 500 >48
Tolazamide 100-1000 12-24
Tolbutamide 500-3000 6-12
Sulfonylurea – second
gen
Glimepride 1-8 24
Glipizide 2.5-40 12-18
Glipizide ER 5-10 24
Glyburide 1.25-20 12-24
Nonsulfonylureas
Repaglinide 0.5-16 2-6
OHA
Biguanides
Metformin is representative
Reduces hepatic glucose production, improves
peripheral glucose utilization
Reduces FPG, insulin levels, improves lipid
profile
A1c reduction 1-2%
Modest weight loss
Initial dose 500 mg OD or BD , (up to 1000 mg
BD)
OHA
Metformin
Side effects- nausea ,vomiting, lactic acidosis
Contraindication
 Serum creat- > 1.5 mg/dl in men , >1.4 mg/dl in
women
 Acidosis, severely ill
 CHF
 Liver disease
 Severe hypoxia
 Nil orally
 Receiving radiographic contrast material
OHA
α glucosidase inhibitors
Acarbose( 50-100)mg& Miglitol (50 mg)
Inhibits enzymes that cleaves oligosaccharides
into simple sugars
Initiated at low dose (25mg) with evening
meals
Reduces A1c by 0.5-0.8%
Side effects
 Diarrhea, flatulence
 Abdominal distention
OHA
α glucosidase inhibitors
Contraindication
 Inflammatory bowel disease
 Gastroparesis
 Serum creatinine > 2.0 mg/dl
 Hypoglycemia ( if used with sulfonylureas)
OHA
Thiazolidinediones
Rosiglitazone(2-8 mg), Pioglitazone ( 15-45mg)
PPARγ agonist
Promote redistribution of fat from central to
peripheral location
Increase insulin sensitivity
Measurement of LFT before initiation & at
regular interval
OHA
Thiazolidinediones
Side effects
 Weight gain (2-3 kg)
 Reduction in hematocrit
 Peripheral edema & CHF ( with insulin)

Contraindication
 Liver diseases
 CHF ( class III or IV )
Parenteral
GLP-1 receptor signal enhancer
Incretins amplify glucose stimulated insulin
secretion
GLP-1 agonist –Exenatide
DPP- IV inhibitor – Sitagliptin
Reduces A1c by 0.5- 0.1%
Parenteral
Exenatide
Bind to GLP-1 receptors in GIT, islets & brain
Increases glucose stimulated insulin secretion
Suppresses glucagon, slows gastric emptying
Approved as combination with metformins or
sulfonylureas, not to be used with insulin
Dose – 5-10µg SC BD before meals
Parenteral
Sitagliptin
Inhibit degradation of native GLP-1
Used with diet, exercise , Metformin or
Thiazolidinediones
Dose -100mg/day PO
Assess renal function prior to initiation
Reduce doses
 50mg OD if creat clearance -30-50 ml/min
 25mg OD if creat clearance < 30ml/min
Parenteral
Pramlintide ( analogue of amylin)
Reduce post prandial glycemic excursions
Slows gastric emptying & suppresses glucagon
Does not alter insulin level
60µg SC before each meal ( Max- 120 µg )
Reduces A1c by 0.25-0.5%
Side effects
 Nausea & vomiting
Parenteral
Insulin
Initial therapy in
 Lean individuals
 Severe weight loss
 Renal or hepatic diseases

Initiated as single dose long acting insulin

(0.3-0.4U/kg/day)
10% Increments as per SMBG
May be used with OHAs
Glycemic control type 2 DM
Initial choice of therapy
Mild to mod hyperglycemia(FPG 200-250mg/dl)
 Single OHA
Severe hyperglycemia ( FPG- >250mg/dl)
 Stepwise approach
 Insulin

Insulin secretagogues & α glucosidase

inhibitors immediately lowers glucose whereas
Biguanides & Thiazolidinediones effect is
delayed by weeks to months
Glycemic control Type 2DM
Complication
Acute
DKA
HHS
Chronic
Microvascular
 Eye disease ( retinopathy, macular edema)
 Neuropathy ( sensory, motor, autonomic)
 Nephropathy
Complications
Chronic
 Macrovascular
 Coronary artery disease
 Peripheral artery disease
 Cerebrovascular disease
 Other
 GI ( gastroparesis, diarrhea)
 Genitourinary ( uropathy, sexual dysfunction)
 Dermatologic
 Infectious
 Periodontal disease
 Cataract/Glaucoma
Complications
Diabetic retinopathy
NPDR ( 25% in 5 years , 80% in 15 years)
Only severe NPDR progresses to PDR
Examination
 3-5 years after Type1 DM
 immediately in Type2 DM
 Then annually

Optimal BP & glycemic control reduces

progression
PDR treated with Panretinal laser
photocoagulation
Complications
Neuropathy
Screened for distal symmetric polyneuropathy
(DPN) at diagnosis and at least annually
thereafter
Simple inspection of insensate feet 3- to 6-
month intervals
Screening for autonomic neuropathy at
diagnosis of type 2 DM and 5 years after the
diagnosis of type 1 DM.
Complications
Neuropathy
Hypertension ,hypertriglyceridemia should be
treated
Avoid alcohol & smoking
Orthostatic hypotension
 Pharmacological(fludrocortisone, midodrine,
clonidine, octreotide , yohimbine)
 Adequate salt intake
 Avoid dehydration, diuretics
 Lower extremity support
Drugs to treat symptomatic DPN
Complications
Nephropathy
 Microalbuminuria
 Type 1 diabetes ≥5 years
 Type 2 diabetic patients, starting at diagnosis

Serum creatinine should be measured at least

annually for the estimation of GFR regardless
of the degree of urine albumin excretion
Complications
Nephropathy –treatment
Protein intake to 0.8 –1.0g/kg /day (early CKD )
& to 0.8 g /kg/day (late CKD)
ACE inhibitors or ARBs (except pregnancy).
Non-DCCBs,β-blockers, or diuretics for BP(if
unable to tolerateACEI and/or ARBs)
Consultation with a nephrologist when the
GFR is 30 ml/min/ 1.73m2.
Complications
CVS
Hypertension
BP measured at every routine diabetes visit
Target goals of 110–129/65–79 mmHg
BP < 125/75mmHg if macroalbuminuria
If SBP 130-139 & DBP 80-89 lifestyle &
behavioural therapy for 3 months
Complication
CVS
Hypertension
ACEI & ARB as first choice( glucose & lipid
neutral/ beneficial)
β-blockers,( can increase insulin resistance)
Diuretics,
Calcium channel blockers( non DHP preferred)
Complications
CVS
Lipids
 LDL 100mg/dl ( without over CVD, <40 years)
LDL<70 mg/dl or 30-40% reduction
( >40yrs,overt CVD)
Triglycerides <150 mg/dl & HDL >40 mg/dl.
( women, HDL > 50 mg/dl )
Lifestyle modification ( MNT, increased
physical activity, weight loss , and smoking
cessation)
Statins
Complications
Antiplatelets ( aspirin -75–162 mg/day)
Secondary prevention strategy if a history of CVD.
 Primary prevention strategy in Type 2&type 1 DM at
increased cardiovascular risk,
 >40 years of age
 Family history of CVD,
 Hypertension,
 Smoking,
 Dyslipidemia,
 Albuminuria
Between the age of 30 and 40 years, in the presence
of other CVD risk factors.
Complications
Screening cardiac stress test
 H/o of peripheral or carotid occlusive
disease
Sedentary lifestyle, age 35 years, and plans
to begin a vigorous exercise program.
Stress nuclear perfusion and stress
echocardiography test if abnormal exercise
ECG
Complication
Gastroparesis
Nausea, vomiting, early satiety, abdominal
bloating
Nuclear scintigraphy after ingestion of
radiolabeled meal is best stud
Treated with
 Smaller , more frequent meals low in fat & fibers
 Dopamine agonists
 Erythromicin
Complication
Diabetic foot
Plantar surface is the most common site
Mild or non limb threatening with oral
antibiotics ( cephalo, clinda, augmentin,
flouroquinolones)
Severe with IV antibiotics ( ertapenem,
piptaz,augmentin, linezolid or clinda + flouro)
Surgical debridement
Local wound care
Future therapy
Autologous Nonmyeloablative Hematopoietic
Stem Cell Transplantation(Type 1 DM)
Renal & pancreas transplantation
Thank
you