Complications of Diabetes

What is Diabetes Mellitus?

Diabainein in greek refers - to pass throughMel refers to- honeyDiabetes- “sweet urine”

Chronic metabolic disorder characterized- persistent hyperglycemia, altered metabolism of lipids, carbohydrates and proteins.

Diagnostic Criteria

American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S5-S10

FPG 2-h PPG (OGTT)

126

60

80

100

120

140

160

180

200

Plasma glucose

(mg/dL)

Normal

Diabetes Mellitus

240

220

Diabetes Mellitus

Normal

IGT

IGT

8

Etiological Classification

I. Type 1 diabetes - previously known as juvenile diabetes

insulin-dependent diabetes mellitus (IDDM)II. Type 2 diabetes - previously known as adult-onset

diabetesnon-insulin-dependent diabetes mellitus (NIDDM)

III. Gestational diabetes mellitus (GDM)

American Diabetes Association

Type- I Diabetes Mellitus

T cell-mediated destruction of pancreatic ß-cells

Rapid onset, usually in childhood

Complete insulin deficiency

Absolute insulin requirement

Type- II Diabetes Mellitus

Pancreas doesn’t produce enough insulin or cells ignore it (insulin resistance)

Most people with diabetes have type 2 (85%), occurs after 40 years of age

Associated with obesity & runs in families to some extent

Lifestyle issues prominent

Gestational Diabetes Mellitus (GDM)

Any degree of glucose intolerance with onset during pregnancy

Return to normal glucose regulation after delivery is common

Increased perinatal morbidity and mortality if untreated

Salient Clinical Symptoms

Disease of mainly three P’s

Polydipsia- Excessive ThirstPolyphagia- Excessive HungerPolyurea- Excessive Urination

Hyperglycemia Tiredness Loss of weight

Diabetes Mellitus - Complications

Complications of diabetes mellitus

Acute (Metabolic) Chronic (Angiopathy)

Macro Vascular Complications

Micro Vascular Complications

Risk factors and complications

Microvascular diseaseEyes

KidneysNerves

Macrovascular diseaseIschaemic heart disease

StrokesPeripheral vascular

disease

Feet

HypertensionHyperglycaemia

DyslipidaemiaCoagulopathy

Smoking

Acute Complications

Diabetic Ketoacidosis (DKA)

Hyperosmolar non-ketomic Coma (HONK)

Hypoglycemia

Metabolic injury to large vessels

Heart Brain Extremities

Coronary artery disease

– Coronary syndrome

– MI– CHF

Cerebrovascular disease Peripheral vascular

disease– Ulceration– Gangrene– Amputation

Biology of Macrovascular Injury

Hyperglycemia

Neuropathy– Peripheral– Autonomic

Kidney Nerves

Retinopathy- Cataract- Glaucoma

Nephropathy– Microalbuminuria– Gross albuminuria

Blindness Kidney failure Amputation

Death and/or disability

Eye

Biology of Microvascular Injury

Microvascular Complications of Diabetes-1

Retinopathy: Damage to blood vessels in and around the retina. It could occur with varying degrees of severity.

Normal ------------- Small hemorrhages --------- Large hemorrhage

Nephropathy: Glomeruli are damaged in the

kidneys. Results in loss of protein DIAGNOSTIC VALUE-Normal

microalbumin level is 30mg/24 hours.

May lead to kidney failure

Microvascular Complications of Diabetes-2

Microvascular Complications of Diabetes-3

Neuropathy

Nerve fibres degenerate Blood vessels supplying the nerves are ‘grossly

diseased’

Mechanism of Complications of Diabetes

Mechanisms causing diabetic complications-1

Accumulation of SorbitolPolyol (Polyhydroxy alcohols) Pathway

Sorbitol is formed from glucose catalyzed by aldose reductase This pathway is activated in hyperglycemia Sorbitol does not cross cell membranes, accumulates

intracellularly and produces osmotic stress. Sorbitol normally helps in osmoregulation

Consequences of high Sorbitol concentration

• Osmotic damage to cells: caused by impermeable Sorbitol intracellularly

• Reduction in nerve myoinositol: causes decrease activity of Na/K ATP Pump- causes decreased nerve conduction velocity

• Inhibition of nitric oxide (NO) production: results in vasoconstriction and hypertension

• Increased production of free radicals: which cause oxidative damage to tissue

Mechanisms causing diabetic complications-2

Glycation of Proteins Sugars in the blood and inside cells form chemical bonds to

proteins and to DNA by glycation or nonenzymatic glycosylation. Over time, the glycated proteins are chemically modified to

become molecular structures called Advanced Glycation Endproducts (AGEs).

Pathological Consequencesof Glycation of Proteins in Diabetics

Crosslinking reduces the flexibility, elasticity and functionality of the proteins.

The chemical modifications of glycation and crosslinking can initiate harmful inflammatory and autoimmune responses.

Glycation has been found in connective tissue collagen, arterial collagen, kidney glomerular basement membrane, eye lens crystallins, nerve myelin proteins and in the circulating low-density lipoprotein (LDL) of the blood.

23

Diabetes is Managed,But it Does Not Go Away.

GOAL:To maintain target blood

glucose

Management Of Diabetes Mellitus

The Fundamental Aim is - Glycemic ControlHbA1C < 7.0%Pre-prandial PG 90 – 130 mg/dlPostprandial PG < 180 mg/dlBlood Pressure < 130/80 mmHgLipids - LDL < 100 mg/dl

Triglycerides < 150 mg/dlHDL > 40 mg/dl

Management Of DM

• Step 1: Diet and Exercise to achieve Euglycemia.

If Euglycemia not achieved; Follow Step 2.• Step 2: Monotherapy with:

– Sulfonylurea– Bigunide– Glitazones– Meglitinides (Repaglinides)– Alpha-glucosidase

• Step 3: Addition of second oral agent or Insulin.Consider Insulin therapy in Type I DM always.

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