Diabetes Mellitus

Diabetes = going through in Greek Mellitus = honey in Latin Definition: It is a group of metabolic diseases characterized by high blood sugar (glucose) levels, that result from an imbalance between insulin availability and insulin need History: First reports at 1st century when Aretaeus the cappadocian described the disorder as a chronic affection with intense thirst and voluminous, honey sweet urine. It is then believed that it is the melting down of flesh into urine.

EPIDEMIOLOGY:
Rates increasing worldwide. At least 171 million people currently

have diabetes estimated 366 million by 2030. Prevalence rates doubled between 1990 and 2005, CDC has characterized the increase as an epidemic . incidence varies substantially in different parts of the world, almost certainly because of environmental and lifestyle factors. The top 5 countries, in numbers of people with diabetes, are currently India, China, the United States, Indonesia, Japan. The greatest increase in rates will occur in Africa the next 20 years.

Types of Diabetes Mellitus

Type 1 insulin dependent or previously called Juvenile DM autoimmune disease destruction of beta cells of the pancreas. exogenous insulin necessary or pancreas transplant . Mostly children (juvenile) but also adults Type 2 non insulin dependent Gestational diabetes(GDM) hyperglycemia during pregnancy Secondary Diabetes Mellitus due to: Pancreas diseases like Chronic pancreatitis, Adenocarcinomas,

Cystic fibrosis, Hemochromatosis, panceatectomy Endocrine like Phaeochromocytoma Somatostatinoma , Glucagonoma Toxins-Drugs(Cushings syndrome) Genetic Defects :Monogenic Diabetes-Maturity onset diabetes of the young (MODY) hereditary form of diabetes mutations in an AD gene (sex independent, i.e. inherited from any of the parents) disrupting insulin production Infections.

Diabetes Mellitus type 2

Diabetes mellitus type 2 or type 2 diabetes (formerly called non-insulin-dependent diabetes mellitus (NIDDM), or adult-onset diabetes) is a disorder that is characterized by high blood glucose caused by insulin resistance and relative insulin deficiency. Accounts for approximately 90% of all cases of diabetes. Considered a disease of adults(usually appears after age of 30) BUT is increasingly diagnosed in children in parallel to rising obesity rates during childhood Early symptoms are subtle. In fact, about one out of three people with type 2 diabetes don't know they have it. Often asymptomatic, The body can adapt to a slow rise in blood glucose to a greater extent than it can to a rapid rise(which happens in DM1).

Clinical manifestation
Look for: Polyuria and polydipsia are the cardinal symptoms of diabetes and occur when the blood glucose level exceeds the renal threshold for glucose excretion - usually approximately 10 mmol/L. Weight loss. Despite polyphagia. Unable to utilize glucose body turns to alternative fuels stored in muscle and fat. Weight loss is a relatively unusual feature in the presentation of T2DM. Weakness and fatigue. Decreased plasma volume leads to postural hypotension; potassium loss and protein catabolism contribute to weakness. cells are deprived of sugar, you become tired and irritable. Blurred vision. is due to osmotically driven swelling of the lens and varies as the degree of hyperglycemia varies. Slow-healing sores or frequent infections. Type 2 diabetes affects your ability to heal and resist infections. genital candidiasis is a prevalent ex Pruritis is a classical symptom of hyperglycemia Areas of darkened skin. condition, called acanthosis nigricans, may be a sign of insulin resistance but is not that common.

Complications

Sustained hyperglycemia leads to chronic toxicity and tissue lesions and eventually diabetic complications Long-term complications of diabetes develop gradually and can eventually be disabling or even life-threatening. Controlling blood sugar levels is the only way to prevent these complications.

Complications include: Macrovascular

y Coronary artery disease(35%)- ischemic heart disease , heart

attack-Death rate from heart disease is at least 3 times higher y Cerebrovascular disease- risk of stroke is 2-4 times higher y Peripheral arterial disease -diabetic foot, atherosclerosis , hypertension

Microvascular
y Neuropathy(18%)-diabetic foot , if untreated, cuts and blisters

can become serious infections. Severe damage require toe, foot or even leg amputation. Damage to the nerves that control digestion can cause problems with nausea, vomiting, diarrhea or constipation. y Nephropathy(2%)- nephrosclerosis , renal failure, This can lead to kidney failure or irreversible end-stage kidney disease, requiring dialysis or a kidney transplant. y Retinopathy(17%)-blurred vision - can lead to blindness. Also risk of cataracts and glaucoma.

Infection-Skin and mouth susceptibility to bacterial and fungal infections. Gum infections especially when poor dental hygiene. Depression Erectile dysfunction- microvascular neuropathy Hypoglycemia Impaired wound healing Diabetic ketoacidosis

Risk Factors:
Controllable: Overweight/central obesity =body mass index (BMI) over 25. Primary risk factor of T2DM since the amount of fatty tissue is related to insulin resistance. Sedentary lifestyle. Low physical activity means greater risk of T2DM development as it helps to control weight, to use up glucose as energy and increases sensitivity to insulin. Dyslipidemia - HDL lower than 35 mg/dL or TGs over 250 mg/dL. Hypertension greater than 140 /90 in adults. Smoking. Steroid therapy: possible to induced diabetes T2DM -treated with oral hypoglycemic Non controllable: Race /ethnicity: Hispanics, African Americans, Native Americans, and Asians higher risk. Family history of diabetes: first-degree relative(parent or sibling) Age: 40 and older increases risk of T2DM. less exercise , lose muscle mass gain weight. Insulin resistance History of impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) Low birth weight may predispose to develop type 2 diabetes mellitus

2 diabetes accounts for approximately 90% of all cases of diabetes. Excess weight and inactivity seem to be contributing factors. During digestion , carbohydrates from diet break down into glucose , a sugar, which is absorbed into the bloodstream. Normally, glucose then enters cells with the help of insulin. Glucose is a main source of energy for the cells that make up muscles and other tissues. It comes from two major sources: the food and the liver. Insulin is a hormone secreted from beta cells of pancreas in response to increased levels of glucose in blood. it acts like a key by unlocking doorways on the cells membrane that allow sugar to enter. Insulin lowers the amount of sugar into bloodstream and keep glucose homeostasis in normal levels has anabolic effects like glycogenesis and proteinsynthesis. The liver acts as a glucose storage and manufacturing center. When insulin levels are low in fasting conditions, for example the liver metabolizes stored glycogen into glucose to keep normal glucose levels.(homeostasis) In type 2 diabetes, insulin resistance is the cardinal pathogenic factor and patients are therefore initially hyper insulinaemic although eventually beta cell failure intervenes. Thus glucose builds up into bloodstream causing serious complications.

Type

Laboratory and Diagnostic Findings

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Normal glucose levels: 4.4 to 6.1 mmol/L (82 to 110 mg/dL) Diabetes screening is recommended for: Overweight children with risk factors for diabetes, starting at age 10 and repeated every 2 years Overweight adults (BMI greater than 25) with other risk factors(sedentary lifestyle, a family history of type 2 diabetes, a personal history of gestational diabetes or blood pressure above 135/80 mm/Hg Adults over age 45 every 3 years Investigatory and diagnostic tests for diabetes follow: Urine sugar test Urine ketone test Blood glucose tests  Oral Glucose Tolerance Test(also glucose challenge test)  FPG-Fasting plasma glucose Test  HbA1c blood test(HbA1c) - Not for diagnosis, but for Ongoing monitoring of glucose control in last 2-3 months. It measures the percentage of blood sugar attached to hemoglobin. The higher the blood glucose levels, the more hemoglobin will be with sugar attached.  Random blood sugar test.

THE FASTING BLOOD GLUCOSE TEST(FBG) One of the best for diagnosis, easy and comfortable. A blood sample will be taken after an overnight fast. ORAL GLUCOSE TOLERANCE TEST (OGTT): It is still a gold standard for diagnosing diabetes and Gestationals diabetes best test. The patient fasts overnight, and the fasting blood sugar level is measured. Then he drinks a sugary liquid, and blood sugar levels are tested periodically for the next several hours. C-RANDOM (NON-FASTING) BLOOD GLUCOSE TEST A blood sample will be taken at a random time regardless of when was the last meal, a random blood sugar level of suggests diabetes, especially when coupled with any of the signs and symptoms of diabetes(polyuria and polydypsia)
mg/dL(mmol/L) Normal Prediabetes Diabetes FBGT <100 (5.6) 100 -125(5.6-6.9) 126(7) or higher on
two separate tests

OGTT/ random GT <140 (7.8) 140-199(7.8-11.0) 200(11.1)

after 2hrs /+DM symptoms

HbA1c in %
<5.7% (DCCT) ( 3.8-5.5%) 3.8-

5.7% - 6.4% 6.5% or higher

Management

Goals:  eliminate symptoms and  prevent/slow down the development of complications.  Microvascular risk reduction is accomplished through control of glycemia and BP;  macrovascular risk reduction, through control of lipids and hypertension, smoking cessation, and aspirin therapy; statin , ACEi  metabolic and neurologic risk reduction, through control of glycemia. Combination of  lifestyle changes  oral hypoglycemic and  eventually insulin therapy becomes unavoidable in the overwhelming majority of cases.

Treatment for type 2 diabetes requires a lifelong commitment to:

y Blood sugar monitoring- blood glucose should be maintained at

near-normal levels of 90-150 mg/dL and hemoglobin A1C [HbA1c] levels < 7%. Education of the patient is of crucial importance y Healthy eating-need plenty of foods which are high in nutrition and decrease saturated fat intake less than 7% of total calories. Increase fiber intake (14gm/day)-vegetables whole grains- as well as less animal products and sweets. Low glycemic index foods also may be helpful.(prefer potato than spaghetti) y Regular exercise and weight control :Regular physical activity150min/week as physical activity lowers blood sugar and burns fat, increases insulin sensitivity and HDL, decreases TG and atherosclerosis. Moderate weight loss of at least 7% is indicated. y Therapies to reduce weight: - Orlistat: lipase inhibitor-reduces absorption of fat-promotes weight loss - Gastric banding and gastric bypass surgery used in intense obesity which does not respond to diets or exercise for more than 6months y Diabetes medication or insulin therapy

 The most common types of medication taken either by

mouth(TABLETS) or injection: Biguanides -Metformin-best primary T for DM2, reduces gluconeogenesis, decreases insulin resistance, continuously used- contraindicated in liver or renal failure Sulfonylureas -secretagogue of insulin, only when remaining beta cells, not in pregnancy- ex. glimepiride, gliclazide, tolbutamide-S.E hypoglycemia, weight gain Thiazolidinediones(glitazones) -reduce insulin resistanceredistribute fat- require insulin to work ex rosiglitazone(risk of heart problems)-pioglitazone. Meglitinides including repaglinide and nateglinidesecretagogues Alpha- glucosidase inhibitors (such as acarbose)-reduce glucose absorption and enter blood Injectable medicines y incretins ( exenatide) y Dipeptidyl peptidase IV inhibitors( vildagliptin , sitagliptin)inhibit breakdown of incretins These drugs may be given with insulin, or as a monotherapy.

Insulin treatment
In type 2 diabetes, there is a gradual decline in beta cell function, so that treatment will need regular adjustment. It is injected under the skin using a syringe or insulin pen device. Not taken by mouth

Insulin regimens:
Basal insulin - this is often a suitable first step, using once- or twice-daily intermediate- or long-acting insulin Twice-daily biphasic insulin Basal-bolus regimen Oral hypoglycaemic agents are often used in combination with insulin Note: glitazones are contra-indicated with insulin. Sulphonylureas are often continued with a basal insulin regimen; however, if a bolus regimen is used, they should be gradually stopped. A second medication may be added within the first two to three months if blood sugar control is not adequate. "Adequate" control is defined as an A1C level less than 7 percent for most people; insulin may be recommended early if the A1C remains elevated despite lifestyle changes and diabetes pills, especially if the A1C is higher than 8.5 percent. Types of Insulin: mostly by subcutaneous injections, two types: y Short acting insulins -little benefit in DM2, derived either by beef and pig either biosynthetic. Used in pumps, in emergencies or multiple doses regimens. Ex are insulin lispo, insulin aspart and insulin glulisine. Features: enter circulation and disappear from it more rapidly than human insulin-no hypoglycemia induction y Long acting insulins - their stracture is modified to delay absorption or prolong duration of action. Ex are insulin glargine and insulin detemir for intensified therapy or hypoglycemia. NPH( isophane insulin) is the golden standard widely used.

PATIENT EDUCATION AND ADVICING-PREVENTION

VERY IMPORTANT!EDUCATED PATIENT MEANS BETTER TREATMENT! Individualized meal plan in meeting weekly weight loss goals and assist with compliance. Assess patients for cognitive or sensory impairments, which may interfere with the ability to accurately administer insulin. Demonstrate and explain the procedure for insulin self-injection. Review dosage and time of injections in relation to meals, activity, and bedtime Instruct patient in the importance of accuracy of insulin preparation and meal timing to avoid hypoglycemia. Explain the importance of exercise in maintaining or reducing weight. Advise patient to assess blood glucose level before strenuous activity and to eat carbohydrate snack before exercising to avoid hypoglycemia. Assess feet and legs for skin temperature, sensation, soft tissues injuries, corns, calluses, dryness, hair distribution, pulses and deep tendon reflexes. Maintain skin integrity Advice patient who smokes to stop smoking or reduce if possible, to reduce vasoconstriction and enhance peripheral flow.

REFERENCES
http://www.nlm.nih.gov/ http://www.mayoclinic.com/ http://emedicine.medscape.com/ http://en.wikipedia.org/ KUMAR AND CLARKS CLINICAL MEDICINE www.uptodate.com/contents/ www.patient.co.uk/doctor/

Thank you!!!