Approach To Dm Pt.

APPROACH TO DIABETES MELLITUS PATIENT PRESENTED BY : Roll No : 648 SHREEJA MAHESHWARI

Hyperglycemia   

Drowsy Flushed Thirsty

Diabetes Mellitus  HYPERGLYCEMIA:

fluid/electrolyte

imbalance. 

Polyuria • Sodium, chloride, potassium excreted

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Polydipsia from dehydration Polyphagia: cells are starving, so person feels hungry despite eating huge amounts of food. Starvation state remains until insulin is available.

Skin problems -Skin Infections leading to boils, carbuncles or abscesses. -Oral & Genital candidiasis

Diabetes Mellitus 

Major risk factors 

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Family history - A history of diabetes in first-degree relatives is a potent risk factor for diabetes. Type 2 diabetes appears to have a stronger genetic component than type 1. Obesity Origin (Afro-American, Hispanic, Native American, Asian-American) Age (older than 45) History of gestational diabetes High cholesterol Hypertension Vascular disease (cerebro-, cardio- or peripheral vascular )

DIET & LIFE STYLE HISTORY • • • • • • • • •

Regularity of meals Content of fatty foods Content of fruits & vegetables Contents of sugary foods Content of salt Alcohol intake Smoking history Occupational history Physical activity

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HISTORY IN DIAGNOSED PATIENTS HOME GLUCOSE TESTING IN PREVIOUSLY DIAGNOSED PTS. INSULIN INJECTIONS – Ascertain whether the patient self injects, delivery device, site chosen, and whether they experience any problems.

SYMPTOMS OF COMPLICATIONS OF DIABETES MACROVASCULAR DISEASE 1. CORONARY HEART DISEASE – Pt. has less severe chest pain symptom known as silent ischemia due to autonomic neuropathy. Only symptom can be breathlessness. 2. PERIPHERAL VASCULAR DISEASE – Pt. present with claudication. There may be foot ulceration. 3. CEREBROVASCULAR DISEASE – Pt. may present with stroke syndrome. TIA are common.

MICROVASCULAR DISEASE RETINOPATHY – May be asymptomatic until it cause significant visual loss, acute due to retinal hemorrhage or insidious due to cataract or maculopathy. 2. NEPHROPATHY – May be asymptomatic until uraemic symptoms ensues like fatigue, breathlessness, tachypnoea, pleuritic chest pain and pruritus. 3. NEUROPATHY – Peripheral sensory neuropathy – numbness, a feeling of walking on cotton wool and paraesthesias or burning, sharp shooting pains. Proximal motor neuropathy (Femoral neuropathy) – uncommon but presents with deep pain and parasthesiae in upper anterior thigh, followed by wasting of quadriceps muscle. Mononeuropathies – particularly affecting the median nerve of the hand (carpal tunnel syndrome ) – This presents with parasthesiae and numbness in the median nerve distribution of the hand (lateral twoand-half digits), and is again worse at night. Similar symptoms may occur in the foot (tarsal tunnel syndrome). Cranial mononeuropathies are rare Autonomic Neuropathy- symptoms includes impotence, gustatory sweating, urinary retention or incontinence, dizziness or syncope due to postural hypotension, constipation or diarrhoea, and nausea vomiting due to diabetic gastroparesis. 1.

EXAMINATION OF THE DAIBETIC PATIENT

Acute hyperglycemic crises – 1. Severely dehydrated with dry mucous membranes and reduced skin turgor. 2. Hypotension and tachycardia 3. Signs of diabetic ketoacidosis Non acute cases : 1. Ascertain BMI 2. Blood pressure – erect and supine 3. Injection sites 4. Dermatological examination 5. Examination of eyes 6. Examination of CVS 7. Examination of Feet

Dermatological examination COMMONLY ENCOUNTERED MANIFESTATIONS     

Skin thickening Microvascular manifestations in the skin . Neuropathy of the foot Infection of the skin in diabetes . Yellow skin and nails

DISTINCT BUT UNCOMMON MANIFESTATIONS  

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Necrobiosis lipoidica Necrobiosis lipoidica is a distinct skin manifestation which is more commonly found in patients who also have diabetes mellitus. Diabetic bullae With no other apparent cause, diabetics may develop blisters, usually on the extremities. Disseminated granuloma annulare Patients who develop disseminated granuloma annulare have been noted to commonly have diabetes mellitus. Kyrle disease An uncommon but distinct finding in diabetic patients with renal disease. Cutaneous side effects of insulin injection Patients who need daily insulin to control their sugar metabolism may develop secondary skin problems.

PEBBLES - ACANTHOSIS NIGRICANS

Anterolateral neck region and dorsum of right hand of a diabetic patient with acanthosis nigricans. It is recognized by the darker velvety skin. The dorsum of the fingers are similarly involved with velvety skin. It is associated with increased epidermal thickness. Velvety appearance consists of multiple closely spaced micropapules.

pebbles - thick skin of diabetes mellitus Although he does not have acanthosis nigricans, he does have similar discrete micropapules located on the knuckle area of this finger.. Proximal nail fold skin of a diabetic patient who demonstrates micropapules or "pebbles" in the absence of acanthosis nigricans. Note that the micropapules in this patient are far less exaggerated than those which occur in acanthosis nigricans. .

Distal inter-phalangeal joint and dorsum of the distal aspect of the left foot diabetic patients demonstrating pebbling. Clinically thickened skin is common on the dorsum of the hand (especially over the knuckles) and sometimes even on the dorsum of the toes.

DIABETIC SCLEREDEMA Occurs in about three percent of diabetics and is almost totally limited to those with adult onset disease. There is visible thickening involving skin on the back of the neck and the upper back.

Diabetic Hand Syndrome Diabetic hand syndrome consists of joint limitations (inability to fully extend a finger) and thickened skin of the hand, especially involving the dorsum of the fingers palpably thickened skin Some patients with diabetes mellitus develop thickening of the skin on the fingers which is termed "scleroderma-like". This terminology does not imply that existence of vasculitis, or Raynaud's phenomenon, only that the skin is thicker.

Joint limitation

In addition to thickened skin, diabetic hand syndrome is characterized by joint limitation. Often diabetics develop asymptomatic joint limitations of the fingers. This limitation is usually minor and not incapacitating. Thick skin and joint limitation seem to correlate with retinopathy.

Diabetic Hand Syndrome The patient's finger on the right is pushing against the examiner's fingers on the left. The finger skin is taught and when the patient pushed, his finger blanched except .for a periungual blush The examiner is attempting to tent the dorsal finger skin which is distal to the proximal interphalangeal joint of this patient . With nondiabetic subjects, it is fairly easy to pick up a fold of skin on the dorsum of the fingers. This is often not the case in persons with diabetes.

The fifth finger demonstrates a typical minor joint limitation. The fifth finger cannot fully . extend

PRAYER SIGN

(CHEIROARTHROPATHY )

The hands of two patients with diabetes mellitus and the diabetic hand syndrome. The patients are attempting to fully appose the palms and fingers. The patient on the left illustrates moderate limitation. The patient on the right has significant impairment.

PERIUNGUAL ERYTHEMA Microvascular disease is a major complication of diabetes mellitus. At the capillary level, this can be due to both a structural (e.g. thickened capillary wall) and functional problems (increased blood viscosity). Impaired blood flow due to increased viscosity results in dilated capillary loops, and such clinical manifestations as facial blush and periungual erythema.

Erythema of the proximal nail fold. Shin of a patient demonstrating hyperpigmented atrophic macules. The patient relates previous trauma for each of these spots.

DERMOPATHY Diabetic dermopathy is a condition characterized by the presence of multiple hyperpigmented atrophic macules on the legs. Typical lesions are depressed (atrophic) and appear to have postinflammatory hyperpigmentation. The occurrence of 4 or more such lesions is almost always limited to persons with diabetes.

PIGMENTED PURPURA Pigmented purpura of the legs is most often encountered in the elderly diabetic. These areas of spontaneous focal extravasation from the microcirculation are recognized as brown to red macules and patches.

Erythematous, brown, and golden macular changes on the shins. The small erythematous areas, representing recent vascular hemorrhage gradually enlarge, turn brown, and coalesce with neighboring lesions. With resolution, the lesion have a golden appearance.

Close-up view of the shin demonstrating the presence of diabetic dermopathy and pigmented purpura. The dermopathy is distinguished by the atrophy whereas the changes involved with pigmented purpura are macular.

SENSORY NEUROPATHY

Another major complication of diabetes mellitus is development of neuropathy. Relative to the skin, the most common manifestations involve legs and feet. Sensory neuropathy allows trauma to occur to the feet from ill-fitting shoes which may then result in ulceration.

callus and ulcer on the distal aspect of the right second toe.

multiple erosions on the dorsal aspect of the toes.

MOTOR NEUROPATHY Motor neuropathy results in weakened intrinsic foot muscles. The toes dorsiflex and the foot splays (becomes wider) on weight -bearing. This new shape may no longer fit the previous shoes and, along with sensory neuropathy, may potentiate trauma and ulceration.

CHARCOT FOOT With loss of sensation and weak intrinsic muscles, the foot may fracture when stressed. Multiple fractures allowed to heal without realignment result in the distortion of shape.

The toes are being drawn upward.

Sensory and motor neuropathy. She started to run bare foot and heard the snapping sound in her feet .

CANDIDA INFECTION Candida albicans is a frequent pathogen in the skin of diabetics usually involving the groin or genital region. Candida involvement of the groin region and uncircumcised penis tend to occur in men who have poor control of their diabetes.

the groin region has erythema and multiple satellite papules

erythema of the glans penis

The hands may also become involved with Candida. Usual sites of infection include proximal nail fold and intertriginous areas which allow for natural moisture to accumulate.

MALIGNANT EXTERNAL OTITIS External otitis is a common, however in diabetics it may become a serious problem. The patient complains of severe ear pain from the otitis. The infection, due to Pseudomonas, may even gain access to cranial nerves. Examination of the ear canal reveals polypoid growths.

STAPHYLOCOCCUS INFECTION Abscess involving the left arm of a diabetic patient. This patient developed a carbuncle at the site of insulin injection.

This patient has an ankle ulcer which developed an erythematous halo and a red streak going up the leg. This vascular ulcer is complicated by cellulitis and lymphangitis

DERMATOPHYTE INFECTION

annular erythematous scaling plaque of dermatophyte infection.

YELLOW NAILS The skin and nails of patients with diabetes tend to take on a yellow hue, probably due to metabolism of glucose which has become linked to protein. YELLOW SKIN Persons with diabetes often have a yellow hue to the skin, best seen on the palms and soles. Probably due to yellow glucosylation endproducts

NECROBIOSIS LIPOIDICA Although necrobiosis is a classic finding in diabetes, it is rather uncommon (less than one percent) and may also occur in persons who do not have the disease. Typical involvement occurs on the legs as bilateral erythematous, brown or yellow plaques with raised margins and central atrophy. The surface of a lesion often becomes somewhat transparent and enlarged blood vessels may be seen in the lesion.

the early papule stage

characteristic translucency and enlargement of underlying cutaneous blood vessels.

SPONTANEOUS BLISTERS IN DIABETES Lesions may rupture, develop an ulcer or become secondarily infected.

DIABETIC NEUROPATHY Diabetic Neuropathy is a common complication of DM. It usually includes micro vascular injury to the small blood vessels leading to your nerves. Diabetic Neuropathy is damage to nerves caused by the prolonged effect of high sugar levels in the blood. Diabetic neuropathy is caused by the walls of the blood vessels that supply the nerves becoming thicker. The end result of this is less nutrients are unable to get to the nerves as well as a demyelinization. This slows the ability of the nerves to conduct impulses back to the brain. The four types are : -Peripheral – that affects the extremities of the body, notably the feet -Autonomic – that affects the autonomic nervous system -Proximal – the areas affects are the hips, thighs and buttocks -Focal – a focused group of nerves in any region of the body.

There are two forms of neuropathies that can form with diabetes; polynueropathies and mononeuropathies.

Polynueropathies are the most common in those with diabetes and is a bilateral sensory disorder. The symptoms for this form are most common in the toes and feet and normally appear there first. Mononeuropathies are isolated events that affect single nerves. The symptoms of this form of neuropathy are entirely dependent on which nerve is affected.

CARPAL TUNNEL SYNDROME

INSULIN INJECTION SITE LIPOATROPHY AND LIPOHYPERTROPHY

DIABETIC NEPHROPATHY Diabetic nephropathy refers to kidney problems which result from diabetes mellitus. These include the excretion of protein in the urine (proteinuria) and slowly developing kidney failure. Diabetes interferes with the function of the glomerular tuft. When enough of these tufts have been affected, kidney failure results.

Proteinuria Most people with established diabetic nephropathy have urine containing large quantities of protein (known as proteinuria), which their doctors can detect using a dipstick urine test.

High blood pressure Another related condition of diabetic nephropathy is high blood pressure (hypertension). Hypertension will speed up existing kidney disease, so treatment of even mild hypertension is necessary for those with diabetes. Because the function of the kidney deteriorates and protein is lost, puffy swelling of the body tissues, especially the legs, can occur. This is called the nephrotic syndrome.

MOUTH COMPLICATIONS Periodontal disease is infection and inflammation of the gums. It can cause gum recession, bone and tooth loss. High blood sugars cause inflammation of the gums and promote infection. Periodontal disease Common signs of periodontal disease are gums that are swollen and bleed easily. Chronic high blood sugar can also cause yeast infections in the mouth and dental caries.

Heart Disease & Stroke Vascular disease can affect all blood vessels in the body. Blocked arteries in the brain can lead to a TIA (transient ischemic attack) or stroke. Blocked arteries in the heart can lead to chest pain (e.g., angina) or a heart attack. Blocked arteries in the legs can cause problems with circulation and walking. Erectile problems also can be due to blocked arteries. Vascular disease It is caused by stiffening and clogging of arteries (atherosclerosis). In diabetes, when the blood sugar is chronically high, excessive amounts of glucose attach to the inner walls of the blood vessels, decreasing their elasticity. Elevated blood sugars also cause atherosclerosis by promoting plaque formation.

DIABETIC RETINOPATHY People with diabetes have an increased chance of developing a variety of eye problems, including cataracts and glaucoma. Typically, changes begin to take place in the retina after a patient has been living with diabetes for 10 to 15 years. The effect of diabetes on the retina and vitreous is called diabetic retinopathy. In the earliest phase of the disease, known as background diabetic retinopathy, the arteries in the retina become weakened and leak, forming small, dot-like hemorrhages. These leaking vessels often lead to swelling or edema in the retina, which may result in decreased vision. The next stage is known as proliferative diabetic retinopathy. In this stage, circulation problems lead to oxygen-deprivation in some areas of the retina. New, fragile, blood vessels develop as the circulatory system attempts to maintain adequate oxygen levels within the retina. This is called neovascularization. The delicate vessels hemorrhage easily and blood may leak into the retina and vitreous, causing spots or floaters, and an overall decrease in vision.

As the disease progresses even further, continued abnormal vessel growth and scarring can result in serious problems such as retinal detachment and glaucoma. Signs and Symptoms •Blurred vision - often linked to blood sugar levels •Floaters and flashes •Sudden loss of vision

DIABETIC CATARACT

Investigations for Diabetes Mellitus Glucose can be estimated chemically and enzymatically. If the fasting blood glucose value is more than 126 mg/dl or the random blood glucose value is more than 200 mg/dl, then it is considered to be a case of diabetes. Glucose Tolernce Test: (GTT) This test is used to measure the glucose tolerance in a person. The blood is drawn at intervals of 30 mins each. The first sample is fasting, at 30 mins, 60 min, 120 mins and 180 mins. In all five samples are collected. The most important role of GTT is to help in the investigation of symptomless glycosuria. Glycosylated Haemoglobin Of all the glycated forms of Hb, HbA1c is the most stable. More than 80 per cent of the glycated form is the HbA1c. Hence, its measurement is taken to be the ideal parameter to understand the “Long term diabetic control”. This is the most important tool for monitoring diabetes. This test refers to the hemoglobin component formed by interaction with glucose, since half life of RBCs is approximately 120 days; a single HbA1c determination can give information about glycemic control in the preceding 8-12 weeks. It is estimated by HPLC method, which is considered to be gold standard. The advantage is that this test does not require any dietary preparations, has low sensitivity but high specificity compared to oral glucose tolerance test.

Microalbumin (MAU) MAU as the name suggests, is the first warning signal to an impending “Nephropathy” - if attention is not paid to keep diabetes under control. Patients with microalbuminuria have a greater risk for developing renal failure, vascular damage and risk for cardiovascular damage. It can be estimated by immunoturbidometry and nephelometry: Insulin This test is used for determination of concentration of bioavailable insulin in the patients. Total insulin exists in free and bound form. In patients without insulin antibodies, total and free levels are similar, but in patients with insulin antibodies total insulin levels are dependant on the binding capacity of the circulating endogenous insulin antibody and availability of insulin to bind to antibody sites. This test is used to determine dosage of IDDM with insulin antibodies. Insulin Antibodies Most common antibodies are IgG, IgM, IgA & IgE Abs have been reported. These antibodies are generally seen in pre-Type I DM as well as DM pts with exogenous bovine or human porcine insulin.

Free Insulin Increased levels of free insulin are seen: Exogenous insulin Insulinoma Insulin resistance Type II DM. Proinsulin Proinsulin is produced in beta cells of pancreas and cleaved into insulin and C-peptide before release into circulation. Increased levels are seen in Insulinomas Severe hypoglycemic hypoinsulinomas Hyperproinsulinemia. Proinsulin inhibits hepatic production of glucose thus useful in type II DM.TG & HDL concentrations improve with proinsulin GAD Antibodies GAD-65 Antibodies: GAD is known as Glutamic Acid Decarboxylase. They are detected in approximately 90 per cent of patients who are newly diagnosed of Type I DM and 80 per cent of pre-diabetic individuals and first degree relative of patients with IDDM. C-Peptide C-peptide is cleaved from proinsulin and released into circulation in the course of insulin biosynthesis. C-peptide is used for assessment of pancreatic islet cell function.

Testing : Fasting Plasma Glucose Test (FPG) - (cheap, fast) *fasting B.G.L. 100-125 mg/dl signals pre-diabetes *>126 mg/dl signals diabetes

Oral Glucose Tolerance Test (OGTT) *tested for 2 hrs after glucoserich drink *140-199 mg/dl signals prediabetes *>200 mg/dl signals diabetes

A.K.A.: Glycated Hemoglobin tests A1C ♦

80 to 90 mg per 100 ml, is the normal fasting blood glucose concentration in humans and most mammals which is associated with very low levels of insulin secretion.

Triad of Treatment Diet

Medication Oral hypoglycemics Insulins

Exercise

Diabetes treatment  Diet   

Lower calorie Fewer foods of “high glycemic index” Spread meals evenly

 Exercise  

Under physician supervision Check glucose prior

Diabetes – Oral Medications 6 Classes :      

Sulfonylureas Biguanides Sulfonylureas and biguanide combination drugs Thiazolidinediones Alpha-glycosidase inhibitors Meglitinides

Sulfonylureas  Stimulate pancreas to secrete insulin 

Glyburide (Diabeta) [Prototype Pro p 393] • Diabenese (chlorpropamide) • Glucotrol (Glipizide), Gliclazide, Glibenclamide

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Mechanism of Action

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Sulfonylureas interact with receptors on pancreatic β -cells to block ATP-sensitive potassium channels This, in turn, leads to opening of calcium channels Which leads to the production of insulin

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Adverse reactions

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Hypoglycemia Water retention/edema Photosensitivity

Biguanides  Decreases liver production of glucose  Decreases intestinal absorption of glucose  Improves cell sensitivity to insulin  Example:  

Metformin

GI upset, flatulence Cardiac (CHF, MI)

Thiazolidinediones  Increase cellular sensitivity to insulin  

Pioglitazone (Actos) Rosiglitazone (Avandia)

Patient should have liver enzymes checked periodically

D-Phenylalanine derivatives  Nateglinide (Starlix)  Rapid onset, short half-life 

Good for those with rapid post prandial rise in blood glucose

Combinations  Glucovance 

Glyburide and Metformin

 Avandamet 

Avandia and Metformin

Αlpha – glycosidase inhibitors

Block enzymes that help digest starches  slowing the rise in B.G.L. - Precose ® (acarbose), - Glyset ® (miglitol)

Meglitinides Stimulate more insulin production ; dependant upon level of glucose present - Prandin ® (repaglinide) - Starlix ® (nateglinide)

Insulin   

Made in beta cells of the pancreas Moves glucose into cells (thus acts like growth hormone in a way) Moves potassium into cells (can buy time in emergencies)

Who need insulin medicine  

Type I diabetes patients whose body produces no insulin. Type 2 diabetes patients that do not always produce enough insulin.

Treatment  subcutaneous injection

Insulin drug evolution Stage 1 Insulin was extracted from the glands of cows and pigs. (1920s)

Stage 2 Convert pig insulin into human insulin by removing the one amino acid that distinguishes them and replacing it with the human version.

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Stage 3 Insert the human insulin gene into E. coli and culture the recombinant E.coli to produce insulin (trade name = Humulin®). Yeast is also used to produce insulin (trade name = Novolin®) (1987).

Recombinant DNA technology has also made it possible to manufacture slightly-modified forms of human insulin that work faster (Humalog® and NovoLog®) or slower (Lantus®) than regular human insulin.

Types of insulin

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Regular insulins

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Insulin analogs

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Pre-mixed insulin

Short peptide mimics SITES OF INJECTION

Regular insulins: 

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Human insulin: Humulin® (from E.coli), Novalin® (from yeast) NPH - neutral protamine Hagedorn (NPH), protamine mixed. Lente® insulin / Ultralente® insullinzinc added

Insulin Analogs: 

Fatty Acid Acylated insulins

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Insulin Lispro (Humalog®) (1996)

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Insulin Aspart (NovoLog®) (2000)

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Insulin Glargine (Lantus®) (2002)

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Insulin Detemir (Levemir®) (Jun.,2005)

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Insulin Glulisine (Apidra®) (Jan., 2006)

Insulin preparations given ONLY with syringes marked in “units”    

Rapid acting (lispro, asparte) Short acting (regular) Intermediate acting (NPH) Long acting  

Ultralente [Glargine/Lantus]

Rapid acting insulin  Lispro (Humolog, Novolog Aspart) 

Onset of action • “15-30” minutes [may come on in 5 minutes…]

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Peak of action • 1 - 2 hours

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Duration • 3 – 4 hours

Short acting insulins  Regular (clear so can be given IV) 

Onset of action • 0.5 to 1 hour

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Peak of action • 2 – 4 hours

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Duration of action • 6 – 8 hours

Intermediate acting insulins  NPH, Lente (chemicals added. Cloudy) 

Onset of action • 1 – 4 hours

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Peak of action • 4 – 12 hours

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Duration of action • 18 – 24 hours

Long acting insulins  Ultralente 

Onset of action • 4 – 8 hours

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Peak of action • 18 hours

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Duration of action • 24 – 36 hours

Once a day insulin  Glargine/Lantus 

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Cannot be diluted or mixed in syringe with any other insulin Slow, steady release Daily dosing [usually at bedtime] Refrigerated or tosses every 14 days

Combination insulins  70/30 (70% NPH and 30% regular)  Humolog 70/30 (Humolog and regular)  Fewer injections  Rotate sites to decrease lipodystrophy

Miscellaneous  Byetta for type II Diabetics taking

sulfonylureas or combination 

Mimics physiologic glucose control • Inhances insulin secretion only in presence of hyperglycemia • Insulin secretion decreases as blood glucose approaches normal

 Neutontin for Diabetic nerve pain

Amino Acid Substitutons A-

B- chain Position

chai n Position Source/ Type

A21

B3

B28

B29

B30

Human

Asn

Asn

Pro

Lys

Thr

Aspart

Asn

Aspartic Lys acid

Thr

Lispro

Asn

Glulisin e

Asn

Glargine

Gly

Detemir

Lys

Lys

Pro

Thr

Pro

Glu

Thr

Pro

Lys

Thr

Lys Myristic acid

B31 And B32

rapid-acting

Arg

long-acting

Dawn Phenomenon vs Somogyi’s effect 

Dawn phenomenon

Blood sugar rises in early morning 

Somogyi’s (rebound) effect

Blood sugar rise in morning as reaction to hypoglycemic episode due to counterregulatory hormone release.