Diabetes Mellitus

Introduction Diabetes is world-wide in distribution and the incidence of both type 1 and type 2 diabetes is rising. This global pandemic principally involves type 2 diabetes and is associated with several contributory factors including increased lon-gevity,Obesity,unsatisfactory diet,sedentary lifestyle, and increasing urbanisation. Moreover type 2 diabetes is also commencing at an earlier age in many populations, and in some ethnic groups,such as Hispanic and Afro-Americans ,is now being observed in children and adolescents.India ,a fast developing nation is invariably set to become the diabetic capital of the World .

** Genetic defects of B cell function Maturity Onset Diabetes in Young (MODY) ** Genetic defects of insulin action. ** Diseases of exocrine pancreas Trauma Pancreatitis Pancreatectomy Cystic fibrosis Fibrocalculous Pancreatopathy Haemochromotosis. ** Endocrinopathies. ** Drug induced or chemical induced ** ** ** ** ** Pentamidine, Nicotinic acid, Glucocorticoids, Diazoxide, Thiazide diuretics.

Definition
Diabetes Mellitus is a pan metabolic disorder characterised by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism due to defects in insulin secretion or insulin action or both.

** Infections etc., 4. Gestational Diabetes mellitus (GDM) Onset / Recognition of glucose intolerance in pregnancy

Symptoms
Polyuria -frequent passage of urine with increased nocturnal frequency. Polydypsia - increased thirst Polyphagia - abnormal excessive appetite Weight loss Associated symptoms and signs : Giddiness or Dizziness Pruritis vulvae or Vaginal candidiasis Delayed wound healing Burning sensation of feet Extreme fatiguability Can present with acute or chronic complications of Diabetes mellitus Classification of Diabetes mellitus: 1. Type 1 Diabetes mellitus B cell destruction; absolute insulin deficiency 2. Type 2 Diabetes mellitus Insulin Resistance / Relative Insulin deficiency 3. Other Specific Types:

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APPROACH TO A NEWLY DIAGNOSED DIABETIC Diet, lifestyle changes, exercise

Ketone
yes

Insulin

Refer Text Control

No Yes

Continue

Conventional insulin

Insulin analogue

Obese

Nonobese

Short acting Long acting Intermediate acting Mixed (more PHYSIOLOGICAl)

Insulin Sensitizers

Insulin Secretogogues Absoluter indication: T1Dm DKA HHS GDM Relative Indicator:

Good Control

Yes

Continue

Combination

Yes

Continue

Newly diagnosed T2DM with symptoms with Hyperglycemia Poor control with OHA Hepatic disease Renal disease Intercurrent illness Allergy to OHA

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Investigations
Diagnosis of Diabetes mellitus: (at least one) Symptoms of Diabetes mellitus and Random Blood Sugar > 200 mg% ( mg / dl ) Fasting blood sugar > 126 mg % on more than one occasion 2 hours Plasma glucose > 200 mg % during oral glucose tolerance test with glucose 75g Glucose (or) 1.75gm / kg glucose in children.

Glipizide 4. Biguanides ** Metformin DRUG DOSE mg / day 1.25-20 2.5-25 1-8 t 1/2 SIDE EFFECTS

Insulin secretogogue (sulfonylureas) Glibenclamide Glipizide Glimepride 10 hours 2-4 hours 9 hours 1.5 - 4.9 hours 16-24 hours Nausea, Vomiting, GI disturbances. Anaemia, weight gain, fluid retention, elevated liver function tests. Hypoglycemia, weight gain.

Diagnostic values
Diabetes Mellitus Impaired Fasting Glucose Fasting blood sugar > 126 mg % Post-prandial blood sugar >200mg% Fasting blood sugar> 100 125 mg %

Insulin sensitizer (Biguanides) Metformin 5002000mg

Newer Drugs (Thiazolidinediones) Pioglitazone 15-45mg

Impaired Post-prandial blood sugar> 140 200 Glucose mg% Tolerance

Treatment
Type 1 Diabetes mellitus: Strict meal plan ** Carbohydrate: 50 - 60% ** Protein: 10 20% ** Fat: 30% (If patient is dyslipidemic, fat should be 15%) ** Caloric intake: 30Kcal / kg Physical exercise Only insulin Type 2 Diabetes mellitus: Strict meal plan Physical exercise Oral hypoglycemic agents Insulin

Contraindications for sulphonyl urea therapy 1. Insulin dependent diabetes mellitus (IDDM) 2. Pregnancy 3. Patients with severe infections 4. Allergic reactions 5. Significant liver and kidney disease 6. Patients undergoing surgery Bi-guanides Mechanism of action of Bi-guanides ** Increases insulin sensitivity ** Increases peripheral glucose uptake ** Decreases hepatic gluconeogenesis ** Inhibition of glucose absorption in intestines Contra-indications to Bi-guanide therapy: 1. Renal failure when creatine clearance < 40 ml / min 2. Arteriography or intravenous urography as intravenous iodinated products may precipitate lactic acidosis on patients with bi-guanides 3. Advanced liver cell failure

Oral hypoglycemic agents

Classification: 1. Sulphonyl ureas 2. B-iguanides 3. Sulphonylureas Glibenclamide

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4. Alcoholism 5. Cardiac diseases 6. Diabetes with significant acute and late complications 7. Pregnancy 8. Old age > 70 years

toxicity to islet cells, improve insulin secretion and possibly make oral hypoglycemic agents more effective. Lean patients or those with severe weight loss. Underlying renal or hepatic disease. Hospitalized or acutely ill patients.

If response to oral hypoglycemics is not adeConsider insulin as initial therapy in patients quate. Consider insulin as initial therapy. with: Fasting plasma glucose >250-300 mg/dl since Algorithm to Insulin Therapy more rapid glycemic control will reduce glucose

Start with intermediate acting insulin (NPH) or a long acting insulin (NPH) or a long acting insulin Glargine or Detemir 10 units at bed time or 0.2 units per kg/weight

If HbA1C > 6.5% and Post prandial glucose values are high > 200 mg/dl

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Algorithm for treatment of patients of Type 2 diabetes

HbAC, PA view

120 mg/dl180 mg/dl.

mg/dl.

HbAC

Target,if not achieved to add thiozolidinedione Tab Pioglitazone 15-30 mg /day. If still inadequate control, then add glucosidase inhibitor Tab Acarbose 25-50 mg with meals or consider insulin at this stage

HbAC

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Medical Nutrition Therapy (MNT)

A non-pharmacological mode of management of diabetes. Medical Nutrition therapy is individualized and should be a tailor made regimen. It is used as a compliment for an oral glucose lowering agent / insulin therapy. Energy Recommendations: This depends on body weight and physical activity. ** 20 kcal/kg Ideal body weight Sedentary worker ** 30 kcal/kg Ideal body weight Moderate worker ** 40 kcal/kg Ideal body weight For heavy worker In obese people Reduce 500 kcal from the calculated energy requirement For under weight Add 500 kcal to the calculated energy requirement ** Of the total kcal, 45-65 % kcal from carbohydrate and 10-25 % kcal from proteins Fat recommendation : 500ml / month of a blend of oils / individual Gingelly oil and any refined vegetable oil could be used (or) Rice brand oil and any refined vegetable oil Fibre recommendation 14gm/1000kcal provided. Fluid recommendation: 8 to 10 glasses / day of water except in LVF, CKD, Cirrhosis etc. MNT in Gestational Diabetes Mellitus: 30 kcal / kg Instant Body weight in first trimester 30 kcal / kg Instant Body weight + 300 kcal/day in IInd and IIIrd trimester Protein - 1gm/kg Instant Body weight + 10gm 196

daily throughout pregnancy Avoid hypocaloric diets in obese GDM Provide compulsory bed time and evening snack to avoid accelerated starvation and nocturnal hypoglycemia Gestational Diabetes mellitus: Strict meal plan Physical exercise Insulin Other specific types Strict meal plan Physical exercise Insulin with or without Oral hypoglycemic agents

Gestational Diabetes mellitus

Definition
Gestational diabetes mellitus is defined as carbohydrate intolerance of variable severity with onset or first recognition during the present pregnancy. Risk for gestational diabetes mellitus: Age more than 25 years Family history of diabetes mellitus History of unexplained fetal loss History of baby being large for gestational age History of congenitally malformed infant Maternal obesity History of Polycystic ovarian disease Polyhydramnios Pre-eclampsia Unexplained intrauterine death Methods of screening; Spot test: Fasting <90 mg% [normal 2 hr postprandial <120 mg% random <105 mg% values] ADA recommends

Methods of screening

Monitoring Glycemic Control Blood glucose fasting and postprandial every three days till glycemia is achieved; then every fortnightly, throughout first and second trimester. Every week in third trimester. Glycemic profile monitoring once in 1st and 2nd trimester and then every month in last trimester.

One step approach

Two step approach

100 gm OGTT

Glucose challenge test

Complications of Diabetes mellitus

Acute complications: Hypoglycemia Diabetic Keto Acidosis (DKA) Diabetes and infections Hyperosmolar Hyperglycemic State (HHKNC)

oral glucose tolerance test with 50 gm of glucose

1 hr value > 130mg %

oral glucose tolerance test with 100 gm of glucose

Chronic complications: Follow the flow chart below

Diagnostic Criteria: Carpentar Coustan (with 100 gm) F - 95 mg % 1 hr 2 hr 3 hr - - - 180 mg % 155 mg % 140 mg %

Chronic complications

Microvascular

Macrovascular

WHO criteria (with 75 gm of glucose ) F - 95 mg % 1 hr 2 hr - - 180 mg % 155 mg %

Neuropathy Nephropathy Retinopathy

Coronary Artery Disease (CAD)

If any two values equals or crosses normal value, it is termed as Gestational Diabetes mellitus. Important Note OGTT value should never be treated.

Hypoglycemia

Definition

Treatment
1. Medical Nutrition Therapy [refer MNT] 2. Insulin is essential if MNT fails to achieve euglycemia Target Glycemic Level Fasting glusose 2 hr postprandial Mean glucose

Hypoglycemia is a clinical emergency occurring in diabetes characterized by either autonomic or neuroglycopenic symptoms (or) biochemically random blood sugar < 70mg, due to antidiabetic agent, food and activity mismatch.

Symptoms

90 mg % 120 mg %

105 mg %

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Autonomic symptoms Tremor Palpitation Sweating Sensation of hunger Neuroglycopenic symptoms Head ache Fatigue Irritability Disturbed vision Mental confusion Personality changes Convulsion,night mares Coma Hypoglycemic symptoms in children Restlessness, rolling (or) frequent falling from the bed Sudden changes in behavior Irritability Crying.

Repeat blood sugar value after hypoglycemia correction and monitor blood sugars

Referral:
If the patient remains unconscious even after dextrose administration refer the patient immediately to higher centre for further evaluation. Important Note Patient Education: Educate patient and his family members about low blood sugars and symptoms Never miss a meal after insulin / Oral hypoglycemic agents Be cautious of unaccustomed physical activity To carry diabetic identity card Always carry simple sugar (biscuits and toffee) to avoid low sugars.

Diabetic Ketoacidosis (DKA)

Symptoms
Suspect DKA in a diabetic patient when he has Altered sensorium Unexplained abdominal pain Nausea Vomiting Breathlessness Increased respiratory rate ( Kussmauls breathing ) Signs of dehydration. Thirst Polyuria

Treatment
Draw blood sample immediately Dextrose supplementation ** Conscious: Oral Glucose, Sugar, Fruit Juice ** Unconscious: 50% Dextrose 100ml IV Stat. Followed by 10% Dextrose then by 5% DNS Maintenance (or) Inj. Glucagon 1mg im if not accessible to intravenous route Patient still remains unconscious ** To rule out cerebral edema ** If present IV mannitol + Inj. Dexamethasone 8mg IV Stop the antidiabetic agents for 3 days in Type 2 Diabetic mellitus patients and recheck blood sugars. In Type 1 Diabetic mellitus patients recheck blood sugars after 6 hrs and adjust insulin dose accordingly. Identify the cause of hypoglycemia If recurrent hypoglycemia, rule out ** Renal function disorder ** Liver function disorder 198

Investigations
Blood glucose [usually >250 mg %] Blood Urea [may or may not be ] Serum Creatinine [may or may not be ] Serum electrocyte [Na or , K or ] Serum Bicarbonate < 10 mmol / l Urine sugar Chest X-ray [positive] Urine Acetone [positive]

 ECG Ultrasonogram abdomen / KUB

Contributing factor Hyperglycemia

Mechanism Alters leucocyte functions Impairs phagocytosis Defective leukocyte adherence Foot trauma Bladder dysfunction Reduced sweating

Effect Predisposes to infection

Treatment
Rehydration with normal saline Hours 1 half hour 1 hour
st

Volume 1L 1L 500 ml-1L 500 ml-1L 500 ml-1L Neuropathy Autonomicneuropathy

2 hr
nd

3rd hr 4 hr
th

Foot infection UTI Infections Dry skin

5th hr Total 1 - 5 hr
st th

3.5-5 L 250-500 ml/hr

6th 12th hr

NS for first 4 hrs Consider half NS thereafter May need to adjust type and rate of fluid administration in the elderly and in patients with cardiac and renal compromise Insulin infusion Start regular insulin infusion at 5 units/hr and titrate infusion depending on blood sugars. Electrolyte imbalance If potassium > 5.5, and if patient is anuric no potassium infusion Avoid rapid correction of ** Dehydration ** Hyperglycemia and ** Electrolyte imbalance. Referral: Refer the patient to a higher centre if: ** Patient is comatose ** Hypotension requiring ionotropic support ** Anuric ** Elevated renal parameters ** Evidence of septicemia

Infection and Organisms Hyperglycemia ketosis syndrome Secondary infections in a diabetic can aggravate hyperglycemia and leading to ketosis analysis.

Hyperglycemic hyperosmolar non-ketotic coma (HHNKC) Definition

It is an acute metabolic complication in middle aged and elderly diabetics with high morbidity and mortality.

Causes
Precipated by Infection Trauma Burns Infarction Hyper-alimentation Drugs like ** Thiazide ** Cimetidine ** Phenytoin and ** Parentral diuretics

Symptoms and signs

Polyuria Polydipsia Severe hyperglycemia (Blood sugar > 600 mg%) Profound dehydration Elevated osmolality Hemianopia, muscle fasciculation, seizures

Diabetes and Infections

Both diabetes and its complications predispose to infections.

Causes

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 Altered sensorium, coma

Distinguishing features between DKA and HHNKC

Criteria Age Respiration Dehydration Consciousness Temperature Blood glucose Blood urea Sodium Pottassium Bicarbonate Ketones DKA Younger Hyperventilation, deep Around 10 % Diminished Normal or low >300 mg/dl 42 70 mg/dl 125 140 mmol/l 3 6.5 mmol/l < 14 mmol/l + + To + + + HHNKC Older Normal, shallow Around 25 % Comatose May be raised > 600 mg/ dl 60 180 mg/dl 130 155 mmol/l 35 mmol/l 16 30 mmol/l 0 to +

Treatment
1. Fluid replacement: normal saline at the rate of 2 litre in 1st 2 hours and 1 litre in another 2 hours 2. Low dose insulin. 3. Correction of electrolytes and hyperosmolality 4. Low-dose heparin to prevent vascular thrombosis intravascular coagulation.

Infection Skin and soft tissue infection Carbuncle Necrotising cellulitis Eye Stye Blepharits ,dacrocystitis Dental sepsis Gingivitis Pyorrhea Ear Malignant Otitis externa Nose Mucor mycosis Lung Pulmonary TB, Bacterial pneumonia Gall Bladder Emphysematous cholecystitis UTI Asymptomatic bacteriuria Emphysematous pyelonephritis Emphysematous cystitis Balanoposthitis Vulvo vaginitis

Organisms Staphlococcus Streptococcus Gram negative clostridium Streptococcus

Treatment Appropriate antibiotics

Appropriate antibiotics

Anaerobes Pseudomonas Rhinocera Fungus Mycobacterium

Appropriate antibiotics Ceftriaxone, Ticarcilin Prognosis bad Anti-tuberculosis treatment

Clostritidia

Appropriate antibiotics

E Coli

Appropriate antibiotics Topical Clotrimazole and oral anti fungals if necessary

Candida

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Micro- vascular complications

Diabetic foot

Classification of Diabetic retinopathy (DR)

Grade 1. Non Proliferative diabetic retinopathy (NPDR) a. None b. Early NPDR c. Mild NPDR Symptoms Normal retina Micro Aneurysms (MA) only MA (+) Retinal haemorrhages and / or Hard exudates (HE) (Extra macular i.e > 1 DD from fovea) Mild NPDR (+) Haemorrhages and or Cotton wool spots (>5) and / or Venous beading / looping (or) IRMA* in one field Moderate NPDR (+) MA / Hages in 4 (or) more fields (OR) f. Very severe NPDR Venous beading / looping in 2 (or) more fields (OR) IRMA * in one quadrant Any two (or) more of the severe category NVE** or <1/2 DD NVD***

Causes
Mostly polymicrobial infection Bacteroids are the commonest group Neuropathy and ischemia lead to DFS

Investigations
1. Blood routine and urine routine 2. Urine culture sensitivity 3. Blood culture sensitivity

Treatment
1. Impatient care 2. Insulin is the treatment of choice except for mild infections 3. Mild infections can be managed with OGLA 4. Always suspect Tuberculosis since Tuberculosis and diabetes are concomitant infections e. Severe NPDR (4/2/1 rule) d. M o d e r a t e NPDR

Diabetic retinopathy
1. Definition and Classification 2. Screening 3. General recommendations 4. Treatment

Definition
Diabetic retinopathy is a micro vascular complication of diabetes affecting the vascularity of the eye. (Retina) 2. Proliferative Diabetic retinopathy (PDR) ** PDR without high risk changes (HRC) ** PDR with HRC

NVE or NVD> DD Pre-retinal and / or vitreous haemorrhages *IRMA Intra Retinal Micro Vascular Abnormalities **NVE New Vessel Elsewhere ***NVD- New Vessel Disc.

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Screening
Dilated and comprehensive examination by an Ophthalmologist

** PDR with HRC ** NVD (or) NVE with Pre retinal haemorrhage and / or Vitreous haemorrhage .

Diabetic nephropathy
T1 DM 5 years after onset of DM T2DM shortly after the diagnosis of DM

Definition
Once in 6 months (follow up)

Frequent follow up if DR is progressing

DR is a highly specific vascular complication of both T1 DM and T2 DM patients The prevalence of retinopathy is strongly related to the duration of diabetes. DR is the most frequent cause of blindness in adults. DR and Pregnancy Eye examination: Once in every trimester, 6 wks. after delivery, upto one year Patients should be counseled on the risk of development and / or progression of DR.

Diabetic Nephropathy is defined as progressive increase in urine albumin, accompanied by rising blood pressure and declining GFR resulting in end stage renal disease associated with retinopathy and increased cardio vascular risk.

Symptoms
Puffiness of face Swelling of legs Abdominal distention Reduced urine output. Signs : Bilateral. pedal edema Renal angle tenderness Abdominal bruit

General Recommendations
Glycemic control: Optimal glycemic control ** Reduced risk and progression of DR. Reduction of HbA1c by 1% ** Reduces the relative risk of development of micro vascular complications by 37% Optimal Blood Pressure Control: ** Reduced risk and progression of DR. Diabetic Nephropathy is associated with DR.

Investigations
Screening for Diabetic Nephropathy Three consecutive urine samples

Blood Urea Serum Creatinine

Treatment
Laser Therapy ** Can reduce the risk of vision loss in patients with high risk changes. Prompt referral of patients. with any level of macular oedma, severe NPDR or any PDR Indications for laser therapy ** Clinically Significant Macular Oedma (CSME) ** Mild (or) Moderate NPDR ** Severe NPDR / PDR with out HRC

Increased Urea with altered sensorium

Referral to a higher centre

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Diabetic Neuropathy
Introduction: Diabetic Neuropathy is the most common complication of Diabetes mellitus. It is a micro-vascular complication ** Endo-neural hypoxia due to involvement of micro vascular disease and vasa nervorum involvement. ** Hyperglycemia plays a dominant role in the pathogenesis of diabetic Neuropathy. Polyneuropathy Sensory Proximal Truncal Motor Mononeuropathy Isolated Cranial Truncal Multiple Autonomic neuropathy Parasympathetic Sympathetic

Cardiovascular system Postural hypotension Painless MI Resting tachycardia

Urogenital Bladder dysfunction. Impotence Retrograde ejaculation

Symptoms of Autonomic Neuropathy

Vasomotor Loss of skin vasomotor response Peripheral vascular changes Dependent edema

Gastro intestinal tract Impaired GI motility Gastric atony Diarrhoea

Hypoglycemia Hypoglycemic unawareness

Treatment
1. Strict glycemic control 2. Most of the following drugs offer only symptomatic relief but dont essentially reverse the disease process ** Tricyclic antidepressants ** Anticonvulsants ** Anti-oxidants ** Topical Capsaicin ** Aldose reductase inhibitors ** Methylcobalamine ** Pre-gabalin Referral Patients with severe sensory motor neuropathy with autonomic neuropathy need referral to a higher centre for further evaluation.

Symptoms
1. Burning, shooting, stabbing pain of both feet 2. Pins and needles sensation 3. Absent sensation to several modalities 4. Numbness of both feet 5. Depressed reflexes 6. Muscle paralysis Clinical Features Types: Large fibre type Small fibre type Large fibre type Unsteady gait Absent reflexes Reduced vibration / position sense Mimics posterior column lesion Small fibre type Pain predominates Variable reflexes Variable position / vibration sense Symptoms Diabetic Autonomic Neuropathy (AN)

Macrovascular complications in Diabetes mellitus

Diabetes mellitus and heart: Introduction : Heart is involved in many ways in diabetic patients and they are 1. Coronary artery disease (CAD) 2. Cardiomyopathy 3. Cardiac autonomic neuropathy 4. Heart failure Coronary Artery Disease (CAD) It is a major macrovascular complication seen in diabetics. There is a two to four fold increased risk of CAD in diabetic patients.

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Symptoms
They can present with ** Acute coronary syndromes ** Classical angina ** Silent ischaemia. Silent ischaemia and infarction are very common in diabetics due to cardiovascular autonomic neuropathy. Atypical symptoms such as ** Confusion ** Dyspnoea ** Restlessness ** Unexplained fatigue ** Sweating should alert the clinician to rule out silent infarction. Diabetes is a risk factor for cardiogenic shock and acute left ventricular failure in the setting of ACS.

** Screen for complications at the time of detection and yearly afterward. Gestational Diabetes mellitus: ** Good prognosis for both mother and child if mother achieves and maintains good glycemic control Specific types ** Depends on etiological factor Note: All patients should be given chronic follow up card/book Patient who need to be started on insulin therapy should be taught for insulin injection technique

Hypothyroidism Causes
Hypothyroidism may be primary; common causes of which are autoimmune, iatrogenic due to I131, antithyroid or lithium treatment and thyroidectomy, or secondary to pituitary or hypothalamic disease.

Investigations
ECG, ECHO, TMT and advanced investigation if required.

Symptoms
Coarse dry skin Hoarseness of voice Facial puffiness, weight gain Cardiac enlargement and/or pericardial effusion, Goiter with or without prolonged relaxation phase of deep tendon reflexes. Myxedema coma is a rare complication of severe hypothyroidism with hypothermia, hypoventilation, hyponatremia, hypoxia, hypercapnia and hypotension.

Treatment
Admission may be required based on the clinical status and ECG changes of the patient. It is safe to switch over to Insulin therapy Drugs ** Aspirin ** Cardio Selective beta blockers ** ACE- Inhibitors ** Statins. Referral: Patient may be stabilised and referred to a higher centre for speciality care.

Investigations
Diagnosis is confirmed by Low serum free T3 and T4 serum TSH raised in thyroid types and low in supra-thyroid types Thyro-peroxidase (TPO) ** Thyro-peroxidase antibodies are seen in 9095 % of patients presenting with autoimmune hypothyroidism

Prognosis
It depends on periodical monitoring and regular follow up: Type I Diabetes mellitus: ** With good glycemic control screen for complications 5 yrs after diagnosis Type 2 Diabetes mellitus:

Treatment
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