Diabetes Mellitus

Insulin, Glucagon and Oral Hypoglycaemic Agents

Control of blood glucose PANCREAS & ITS ENDOCRINE ROLE • It functions as both an exocrine as well as an endocrine gland • Located in the curve of the duodenum. • Roughly 99% of the pancreatic cells are arranged in clusters called acini that produce digestive enzymes, • Scattered among the acini are the 1-2 million tine cluster of endocrine tissue called pancreatic islets or islets of Langerhans .

Microscopic picture of islet of Langerhans

An inflammation of body tissue (especially that below the skin) characterized by fever and swelling and redness and pain

Hormones secreted by pancreas • Each islet contains 4 types of hormone producing cells.    

α or A cells – Secrete GLUCAGON β or B cells – Secrete INSULIN δ or D cells – Secrete SOMATOSTATIN F cells – Remainder of the pancreatic islet cells & secrete PANCREATIC POLYPEPTIDE

• Glucagon elevates the blood glucose levels • Insulin lowers the blood glucose level • Somatostatin acts in a paracrine manner to inhibit both insulin and glucagon release from neighboring beta and alpha cells. • Pancreatic polypeptide somatostatin secretion

Regulation of glucagon & insulin secretion Hypoglycemia Hyperglycemia .

Glucagon &

glucagon secretion (Glucose Glycogen) Insulin secretion

. Entry of glucose into cells especially skeletal muscle & its utilization; speed Glycogenesis in the liver . Increase cellular uptake of amino acids & protein synthesis . Speed Lipogenesis , Gluconeogenesis & glycogenolysis

Other stimuli that cause insulin release • • • • •

hGH (Human growth hormone) ACTH Acetylcholine Arginine& Leucine (amino acids in meals) Adrenaline

Factors regulating insulin secretion

Diabetes Mellitus Diabetes Mellitus is a chronic metabolic disorder characterized by hyperglycemia due to an absolute or relative lack of insulin or to a cellular resistance to insulin

Hyperglycemia :• There is an inability of a cell to oxidize carbohydrates due to disturbance in insulin secretion/function. • High blood glucose concentration (fasting plasma glucose > 7.0 mmol/l (126mg/dl), or plasma glucose > 11.1 mmol/l (200mg/dl), 2 hours after a meal)

Diabetes Mellitus Diabetes is any disorder characterized by :• • • • • • • • •

excessive urine secretion hyperglycemia, glucosuria, ketosis, ketonuria, Polyuria Polydypsia (excessive thirst) Polyphagia (excessive hunger) Muscle wasting

Diabetes Mellitus Impact on health of population • Sixth leading cause of death due to cardiovascular effects resulting in atherosclerosis, coronary artery disease, and stroke • Leading cause of end stage renal failure • Major cause of blindness • Most frequent cause of non-traumatic amputations • Diabetes affects estimated 15.7 million people (10.3 million are diagnosed; 5.4 million are undiagnosed) • Increasing prevalence of Type 2 Diabetes in older adults and minority groups (African American, American Indian and Hispanic populations)

Type of Diabetes Mellitus • Type I Diabetes (insulin-dependent diabetes mellitus, IDDM) – characterized by severe insulinopenia and dependence on exogenous insulin to prevent ketosis and to preserve life – onset occurs predominantly in childhood – probably has some genetic predisposition and is likely autoimmune-mediated

• Type II Diabetes (non-insulin-dependent diabetes mellitus, NIDDM) – patients are not insulin dependent and rarely develop ketosis

Type of Diabetes Mellitus – generally occurs after age 40, and there is a high incidence of associated obesity – insulin secretion generally adequate; insulin resistance is present – no associated genetic predisposition

• Secondary Diabetes – occurs in response to other disease processes: • exocrine pancreatic disease (cystic fibrosis) • Cushing syndrome • poison ingestion (rodenticides)

Type I Diabetes Mellitus • Metabolic condition in which the beta cells of pancreas no longer produce insulin; characterized by hyperglycemia, breakdown of body fats and protein and development of ketosis • Accounts for 5 – 10 % of cases of diabetes; most often occurs in childhood or adolescence • Formerly called Juvenile-onset diabetes or insulindependent diabetes (IDDM) Pathophysiology • Autoimmune reaction in which the beta cells that produce insulin are destroyed • Alpha cells produce excess glucagons causing hyperglycemia

Type I Diabetes Mellitus Risk Factors • Genetic predisposition for increased susceptibility • Environmental triggers stimulate an autoimmune response • Viral infections (mumps, rubella, coxsackievirus B4) • Chemical toxins Manifestations • Process of beta cell destruction occurs slowly; hyperglycemia occurs when 80 – 90% is destroyed; often trigger stressor event (e. g. illness)

Type I Diabetes Mellitus •

Hyperglycemia leads to

Polyuria (hyperglycemia acts as osmotic diuretic) Glycosuria (renal threshold for glucose: 180 mg/dL) Polydipsia (thirst from dehydration from polyuria) Polyphagia (hunger and eats more since cell cannot utilize glucose)  Weight loss (body breaking down fat and protein to restore energy source  Malaise and fatigue (from decrease in energy)  Blurred vision (swelling of lenses from osmotic effects)    

Type I Diabetes Mellitus Diabetic Ketoacidosis (DKA) • •

•   

Results from breakdown of fat and overproduction of ketones by the liver and loss of bicarbonate Occurs when Diabetes Type 1 is undiagnosed or known diabetic has increased energy needs, when under physical or emotional stress or fails to take insulin :- Mortality as high as 14% Pathophysiology Hypersomolarity (hyperglycemia, dehydration) Metabolic acidosis (accumulation of ketones) Fluid and electrolyte imbalance (from osmotic diuresis)

Type I Diabetes Mellitus Diagnosis • Patient is symptomatic plus • Casual plasma glucose (non-fasting) is 200 mg/dl OR • Fasting plasma glucose of 126 mg/dl or higher OR • Two hour plasma glucose level of 200 mg/dl or greater during an oral glucose tolerance test

Diagnostic tests • Blood glucose greater than 250 mg/dL • Blood pH less than 7.3 • Blood bicarbonate less than 15 mEq/L • Ketones present in blood • Ketones and glucose present in urine • Electrolyte abnormalities (Na, K, Cl) • Serum osmolality < 350 mosm/kg (normal 280-300)

Type 2 Diabetes Mellitus • Characterized by chronic hyperglycemia • Condition of fasting hyperglycemia occurring despite availability of body’s own insulin • Generally arises from a combination of insulin resistance and β -cell dysfunction • Was known as non-insulin dependent diabetes or adult onset diabetes Pathophysiology • Sufficient insulin production to prevent DKA; but insufficient to lower blood glucose through uptake of glucose by muscle and fat cells • Cellular resistance to insulin increased by obesity, inactivity, illness, age, some medications

Type 2 Diabetes Mellitus What is insulin resistance? • Major defect in individuals with type 2 diabetes • Reduced biological response to insulin • Strong predictor of type 2 diabetes • Closely associated with obesity What is β -cell dysfunction? • Major defect in individuals with type 2 diabetes • Reduced ability of β -cells to secrete insulin in response to hyperglycemia

Insulin resistance and β -cell dysfunction are core defects of type 2 diabetes Genetic susceptibility, obesity, Western lifestyle

Insulin resistance

β

IR

Type 2 diabetes

β -cell dysfunction

Insulin resistance – reduced response to circulating insulin Insulin resistance

Liver

IR Adipose tissue

Muscle

↑ Glucose output

↓ Glucose uptake

↓ Glucose uptake

Hyperglycemia

Type 2 Diabetes : Complex pathophysiology Dual defects → bipolar disease

Carbohydrate DIGESTIVE ENZYMES

Excessive fatty acid release

Glucose

(G) I e s o Gluc

I

I

I

Liver

G

I

I

Adipose Tissue

I G

G

G

Partial defect of insulin secretion

G

G

Pancreas

I

(I)

Excess glucose production

I

G G

Insulin

G

Defective β −cell secretion

G

G

Reduced Glucose uptake

Muscle Resistance to the action of insulin

Type 2 Diabetes Mellitus Risk Factors • • • •

History of diabetes in parents or siblings Obesity (especially of upper body) Physical inactivity Race/ethnicity: African American, Hispanic, or American Indian origin • Women: history of gestational diabetes, polycystic ovary syndrome, delivered baby with birth weight > 9 pounds • Clients with hypertension; HDL cholesterol < 35 mg/dL, and/or triglyceride level > 250 mg/dl.

Diabetes Mellitus • Syndrome X or Metabolic Syndrome – Chronic, low grade inflammatory process – Gives rise to diabetes type 2, ischemic heart disease, left ventricular hypertrophy – Group of disorders with insulin resistance as the main feature – Includes • • • •

Obesity especially around the waist and abdomen Low levels of physical activity High blood pressure Increased blood cholesterol (high LDL, low HDL, high triglycerides

More than 80% of patients progressing to type 2 diabetes are insulin resistant Insulin sensitive; low insulin secretion (16%) Insulin sensitive; good insulin secretion (1%)

Insulin resistant; good insulin secretion (29%)

Insulin resistant; low insulin secretion (54%)

Diabetes Mellitus Manifestations 1. Client usually unaware of diabetes • Discovers diabetes when seeking health care for another concern • Most cases aren’t diagnosed for 5-6 years after the development of the disease • Usually does not experience weight loss 2. Possible symptoms or concerns • Hyperglycemia (not as severe as with Type 1) • Polyuria • Polydipsia • Blurred vision • Fatigue • Paresthesias (numbness in extremities) • Skin Infections

Diabetes Mellitus 3. • • • • • • • • • •

Specific manifestations Cool, clammy skin Rapid heartbeat Hunger Nervousness, tremor Faintness, dizziness Unsteady gait, slurred and/or incoherent speech Vision changes Seizures, coma Severe hypoglycemia can result in death Clients taking medications, such as beta-adrenergic blockers may not experience manifestations associated with autonomic nervous system • Hypoglycemia unawareness: clients with Diabetes Type 1 for 4 or 5 years or more may develop severe hypoglycemia without symptoms which can delay treatment

Diabetes Mellitus Complications of Diabetes A. Alterations in blood sugars: hyperglycemia and hypoglycemia B. Macrocirculation (large blood vessels) • Atherosclerosis occurs more frequently, earlier in diabetics • Involves coronary, peripheral, and cerebral arteries C. Microcirculation (small blood vessels) • Affects basement membrane of small blood vessels and capillaries • Involves tissues affecting eyes and kidneys D. Prevention of complications • Managing diabetes • Lowering risk factors for conditions • Routine screening for complications • Implementing early treatment

Diabetes Mellitus Complications Affecting Cardiovascular System, Vision, and Kidney Function A. Coronary Artery Disease 1. Major risk of myocardial infarction in Type 2 diabetics Increased chance of having a silent MI and delaying medical treatment

2. Most common cause of death for diabetics (40 – 60%) 3. Diabetics more likely to develop Congestive Heart Failure B. Hypertension 1. Affects 20 – 60 % of all diabetics 2. Increases risk for retinopathy, nephropathy

Diabetes Mellitus C. Stroke: •

Type 2 diabetics are 2 – 6 times more likely to have stroke as well as Transient Ischemic Attacks (TIA) or mini stroke

D. Peripheral Vascular Disease 1. Increased risk for Types 1 and 2 diabetics 2. Development of arterial occlusion and thrombosis resulting in gangrene 3. Gangrene from diabetes most common cause of non-traumatic lower limb amputation

Diabetes Mellitus Diabetic Retinopathy 

Retinal changes related to diabetes Hemorrhage, swelling, decreased vision



Leads to retinal ischemia and breakdown of bloodretinal barrier Leading cause of blindness ages 25 – 74

• •

Affects almost all Type 1 diabetics after 20 years Affects 60 % of Type diabetics



 Diabetics should be screened for retinopathy and receive treatment (laser photocoagulation surgery) to prevent vision loss (Should be sent immediately to ophthalmologist upon diagnosis because may already have damage)

 Diabetics also have increased risk for cataract development

Diabetes Mellitus Diabetic Nephropathy • Glomerular changes in kidneys of diabetics leading to impaired renal function • First indicator: microalbuminuria • Diabetics without treatment go on to develop hypertension, edema, progressive renal insufficiency –

In type 1 diabetics, 10 – 15 years – May occur soon after diagnosis with type 2 diabetes since many are undiagnosed for years

• Most common cause of end-stage renal failure in U.S. • Kimmelstiel-Wilson syndrome: glomerulosclerosis associated with diabetes

Diabetes Mellitus Other Complications from Diabetes A. Increased susceptibility to infection • Predisposition is combined effect of other complications • Normal inflammatory response is diminished • Slower than normal healing B. Periodontal disease C. Foot ulcers and infections: predisposition is combined effect of other complications D. Male erectile dysfunction • Half of all diabetic men have erectile dysfunction

Diabetes Mellitus Collaborative Care A. Based on research from 10-year study of Type 1 diabetics conducted by NIH focus is on keeping blood glucose levels as close to normal by active management interventions; complications were reduced by 60% B. Treatment interventions are maintained through • Medications • Dietary management • Exercise C. Management of diabetes with pancreatic transplant, pancreatic cell or Beta cell transplant is in investigative stage

Diabetes Mellitus Diagnostic tests to monitor diabetes management 1. Fasting Blood Glucose (normal: 70 – 110 mg/dL) 2. Glycosylated hemoglobin (c) (Hemoglobin A1C)

• Considered elevated if values above 7% • Blood test analyzes excess glucose attached to hemoglobin. Since RBC lives about 120 days gives an average of the blood glucose over previous 2 to 3 months – Not a fasting test, can be drawn any time of the day – % of glycated (glucose attached) hemoglobin measures how much glucose has been in the bloodstream for the past 3 months

)

Diabetes Mellitus 3. Urine glucose and ketone levels (part of routine urinalysis) • Glucose in urine indicates hyperglycemia (renal threshold is usually 180 mg/dL) • Presence of ketones indicates fat breakdown, indicator of DKA; ketones may be present if person not eating 4. Urine albumin (part of routine urinalysis) • If albumin present, indicates need for workup for nephropathy • Typical order is creatinine clearance testing 5. Cholesterol and Triglyceride levels • LDL < 100 mg/dl, HDL > 45 mg/dL, TG < 150 mg/dL • Monitor risk for atherosclerosis and CVS complications 6. Serum electrolytes in clients with DKA or HHNS

Treatment of Diabetes Mellitus 1. • • 2. • • 3. •

Non-medicine treatment Regular mild to moderate exercise Controlled diet Treatment of IDDM Insulin replacement therapy (a must) Insulin + Oral hypoglycemic agents (sometimes) Treatment of NIDDM Oral hypoglycemic agents

Treatment of Diabetes Mellitus Medications - Insulin Clients who need insulin as therapy: • All type 1 diabetics since their bodies essentially no longer produce insulin • Some Type 2 diabetics, if oral medications are not adequate for control (both oral medications and insulin may be needed) • Diabetics enduring stressor situations such as surgery, corticosteroid therapy, infections, treatment for DKA • Women with gestational diabetes who are not adequately controlled with diet • Some clients receiving high caloric feedings including tube feedings or parenteral nutrition

Insulin • For there is evidence that precise control of blood glucose , with using insulin, is imp. for preventing the long-term complications which are responsible for the morbidity and mortality associated with DM. • Insulin is assayed by using biological method and its quantity is expressed in terms of ‘units’ • 1 Unit = Amount of insulin that is required to reduce blood conc. of glucose in fasting rabbits by 45 mg/dl. • Insulin preparations, commonly available in India, are in strengths of 40 IU/ml and 100 IU/ml

Some physiological aspects of insulin Insulin release in response to blood glucose Release of preformed insulin (Phase I) Phase II NORMAL NIDDM IDDM

0 15 30 45 60 75 min (Time for which glucose was infused)

Insulin • Insulin preparations – Bovine, Porcine, or Human • Insulin, used clinically, is extracted from bovine or porcine pancreatic tissue and is not identical with the human hormone. • Bovine insulin differs in three amino acid residues and pork insulin in one. • Bovine insulin preparations are most antigenic whereas the Human insulin preparations are least. • The use of techniques involving chain recombinant DNA in bacteria is (crb) insulin and enzymatic techniques to modify pork insulin (emp insulin). • Crystalline, soluble insulin has rapid but short-lived action. It can be given intravenously • Longer-acting insulin preparations (lente, semilente, ultralente) are insoluble and are given by s.c. route.

Insulin • When rapid acting or short acting insulin is mixed with longer acting insulin, draw the short acting insulin into the syringe first. • Prevents contamination of the shorter acting insulin with the longer acting insulin • Insuling glargine (Lantus) should not be mixed with any other insulin • Insulin preparations should always be stored at a temp. of 2-80 C • Injection sites – Abdominal areas is the most preferred because of rapid absorption – Do not aspirate insulin injections – Administration covered in the lab

Insulin

Insulin - Injection Sites

Type of Insulin TYPE

Appea- Added Buffer Action (Hours) rance protein Onset Peak Duration

RAPID Regular (cryst.) Semilente

Clear

None

Cloudy None

None

0.3-0.7 2-4

Acetate 0.5-1

5-8

2-8

12-16

INTERMEDIATE NPH (Isophane)

Cloudy Protam. Phosph. 1-2

6-12

18-24

Lente

Cloudy None

Acetate

6-12

18-24

Ultralente

Cloudy None

Acetate 4-6

16-18

20-36

Protamine zinc

Cloudy Protam. Phosph. 4-6

14-20

24-36

1-2

SLOW

Insulin • Alternative insulin administration – Insulin pump • Continuous subcutaneous infusion of a basal dose with increases at meal times

– Implanted pumps • Implanted into the peritoneal cavity

– Inhaled insulin • Under development

MECHANISM OF ACTION OF INSULIN Insulin binding to its receptors located on the surface of its target cell Aggregation of insulin-occupied receptors Endocytosis of insulin Intracellular actions of insulin

Insulin signalling pathways

Summary of insulin effects on metabolism Liver cells Carbohydrate metabolism

gluconeogenesis glycogenolysis

Fat cells glucose uptake glycerol synth.

glycolysis

Muscle glucose uptake glycolysis glycogenesis

glycogenesis Fat metabol.

lipogenesis

Prot. Metabol.

prot. Breakdown

synth. of TGs. fatty acid syth. __

am. acid uptake prot. Synth.

Overview of insulin action Fatty acids

Glucose

Amino acids

TGs Adipose tissue

Glycogen Liver

Protein Muscle

Fatty acids

Clinical uses of insulin • Patients with type 1 diabetes require long-term insulin: – an intermediate-acting preparation (e.g. isophane insulin) is often combined with soluble insulin taken before meals. • Soluble insulin is used (intravenously) in emergency treatment of hyperglycaemic emergencies (e.g. diabetic ketoacidosis). • Many patients with type 2 diabetes ultimately need insulin. • Short-term treatment of patients with type 2 diabetes or impaired glucose tolerance during intercurrent events (e.g. operations, infections, myocardial infarction). • During pregnancy, for gestational diabetes not controlled by diet alone. • Emergency treatment of hyperkalaemia: insulin is given with glucose to lower extracellular K+ via redistribution into cells.

Insulin ADVERSE EFFECTS • Insulin resistance (rare) due to development of insulin antibodies • Allergic reactions • Insulin induced hypoglycemic shock (in case of overdose), coma, death. DRUG INTERACTIONS • Drugs which decrease hypoglycemic effects of insulin Oral contraceptives, Corticosteroids, Diltiazem, Smoking, Thiazide diuretics. • Drugs which increase hypoglycemic effects of insulin Propranolol, Anabolic steroids, Salicylates

Treatment of Diabetes Mellitus Oral Hypoglycaemic Agents • Used to treat Diabetes Type 2 • Client must also maintain prescribed diet and exercise program; monitor blood glucose levels • Not used with pregnant or lactating women • Several different oral hypoglycemic agents and insulin may be prescribed for the client • Specific drug interactions may affect the blood glucose levels • Must have some functioning beta cells

Oral Hypoglycaemic Agents Classification of OHA • Sulfonylureas :Glipizide (Glucotrol), Chlorpropamide (Diabinese), Tolazamide (Tolinase)

• Meglitinides :Repaglinide (Prandin), Nateglinide (Starlix)

• Biguanides :Metformin (Glucophage)

• Alpha-glucoside Inhibitors :Acarbose (Precose), Miglitol (Glyset), Voglibose

• Thizaolidinediones (Glitazones) :Rosiglitazone (Avandia), Pioglitazone (Actos)

Oral Hypoglycaemic Agents Sulfonylureas •

Sulfonylureas that stimulate insulin secretion (e.g. tolbutamide, glibenclamide) – can cause hypoglycaemia (which stimulates appetite and leads to weight gain) – are effective only if β-cells are functional – block ATP-sensitive potassium channels in β-cells – Stimulates pancreatic cells to secrete more insulin and increases sensitivity of peripheral tissues to insulin – Used: to treat non-obese Type 2 diabetics – are well tolerated but promote weight gain

Oral Hypoglycaemic Agents Meglitinides • Meglitinides (Repaglinide,Nateglinide) – Act, like the sulfonylureas, by blocking the sulfonylurea receptor on KATP channels in pancreatic B cells and stimulates pancreatic cells to secret more insulin. – Much less potent than most sulfonylureas (with the exception of tolbutamide), and has rapid onset and offset kinetics. – Rapid absorption (time to maximal plasma concentration approximately 55 minutes after an oral dose) and elimination (half-life approximately 3 hours), short duration of actiona (low risk of hypoglycaemia) – Taken just before meals, – Used in non-obese diabetics

Oral Hypoglycaemic Agents Biguanides •

Biguanides (e.g. metformin): – have complex peripheral actions in the presence of residual insulin, increasing glucose uptake in striated muscle and inhibiting hepatic glucose output and intestinal glucose absorption – Metabolized by the kidney, do not use with renal patients – cause anorexia and encourage weight loss – can be combined with sulfonylureas. – Used in obese diabetics – Does not stimulate insulin release

Oral Hypoglycaemic Agents Alpha-glucoside Inhibitors •

α-Glucosidase inhibitor: Acarbose, Miglitol, Voglibose – Reduces carbohydrate digestion and delay rate of glucose absorption – Take with first bite of the meal or 15 min. after – Adjunct to diet to decrease blood glucose levels – causes flatulence and diarrhoea

Oral Hypoglycemic Agents Thizaolidinediones (Glitazones) • Thiazolidinediones (e.g. rosiglitazone, pioglitazone) – increase insulin sensitivity and lower blood glucose in type 2 diabetes – Sensitizes peripheral tissues to insulin :- Improves sensitivity to insulin in muscle, and fat tissue – Inhibits glucose production – are peroxisome proliferator-activated receptor-γ (a nuclear receptor) agonists. – can cause weight gain and oedema

The dual action of thiazolidinediones reduces HbA1c

Insulin resistance

IR

+ HbA1c

β

β -cell function

Oral Hypoglycaemic Agents • Patients with Type 2 DM who are obese have insulin resistance, they produce enough insulin – Should use Glucophage, Actos or Avandia – Enhances insulin secretion in tissue, but does not increase amount of insulin secreted

• Patients with Type 2 DM who are thin do not produce enough insulin, they are not insulin resistant – Need sulfonylurea agents like Diabinese, Tolinase, Glucotrol, Diabeta

Primary sites of action of oral hypoglycaemic agents α -glucosidase inhibitors

Sulfonylureas/ meglitinides

↓ Carbohydrate breakdown/ absorption

↑ Insulin secretion

Biguanides

Thiazolidinediones

↓ Glucose output ↓ Insulin resistance

↓ Insulin resistance

Clinical uses of oral hypoglycaemic agents • Type 2 diabetes mellitus, to reduce symptoms from hyperglycemia (e.g. thirst, excessive urination). • Metformin is preferred for obese patients unless contraindicated by factor(s) that predispose to lactic acidosis (renal or liver failure, heart failure, hypoxaemia). • Acarbose (α-glucosidase inhibitor) reduces carbohydrate absorption; it causes flatulence and diarrhoea. • Drugs that act on the sulfonylurea receptor (e.g. tolbutamide, glibenclamide) are well tolerated but often promote weight gain.

Treatment of Diabetes Mellitus Role of Diet in Diabetic Management A. Goals for diabetic therapy include • Maintain as near-normal blood glucose levels as possible with balance of food with medications • Obtain optimal serum lipid levels • Provide adequate calories to attain or maintain reasonable weight

B. Diet Composition • Carbohydrates: 60 – 70% of daily diet – Carbohydrates convert quickly to sugars • Advice patient to consume a similar amount of carbs at each meal • Medications can work on a consistent glucose response from foods

• Protein: 15 – 20% of daily diet • Fats: No more than 10% of total calories from saturated fats

Treatment of Diabetes Mellitus • • • •

Fiber: 20 to 35 grams/day; promotes intestinal motility and gives feeling of fullness Sodium: recommended intake 1000 mg per 1000 kcal Sweeteners approved by FDA instead of refined sugars Limited use of alcohol: potential hypoglycemic effect of insulin and oral hypoglycemics

C. Diet •

Look for more dietary information online at http://www.diabetes.org/nutrition-andreceipes/nutrition/overview.jsp

Treatment of Diabetes Mellitus Care of diabetic older clients • 40% of all clients with diabetes are over age of 65 • Need to include spouse, members of family in teaching who may assist with client meeting medical needs • Diet changes may be difficult to implement since client has established eating habits • Exercise programs may need adjustment to meet individual’s abilities (such as physical limitations from other chronic illnesses) – Obesity worsens diabetes – Minimum of 30 minutes of moderate exercise like walking or swimming most days of the week

Treatment of Diabetes Mellitus • Individual reluctance to accept assistance to deal with chronic illness, assist with hygiene • Limited assets for medications, supplies, dietary • Visual deficits or learning challenges to learn insulin administration, blood glucose monitoring • Assisting clients with problem-solving strategies for specific concerns • Providing information about diabetic resources, community education programs, and support groups • Utilizing any client contact as opportunity to review coping status and reinforce proper diabetes management and complication prevention

Diabetes insipidus • Chronic excretion of very large amounts of pale urine of low specific gravity, causing dehydration and extreme thirst • Ordinarily results from inadequate output of pituitary antidiuretic hormone; may be mimicked as a result of excessive fluid intake, as in psychogenic polydipsia • Disorder of ADH secretion, which can be – Neurogenic : due to reduced secretion of ADH – Nephrogenic : due to impaired response of the nephron to ADH

• Some drugs (lithium, demeclocycline, colichcine, vinca alkaloids) cause diabetes insipidus

Glucagon • Glucagon is a single-chain polypeptide of 21 amino acid residues. • Glucagon is a fuel-mobilising hormone, stimulating gluconeogenesis and glycogenolysis, also lipolysis and proteolysis. It increases blood sugar and also increases the force of contraction of the heart. SYNTHESIS, SECRETION AND ACTION • Glucagon is synthesised mainly in the A cell of the islets, but also in the upper GIT. It has considerable structural homology with other gastrointestinal tract hormones, including secretin vasoactive intestinal peptide and GIP. One of the main physiological stimuli to glucagon secretion is the concentration of amino acids, in particular L-arginine, in plasma.

Glucagon • Sympathetic nerve activity and circulating adrenaline stimulate glucagon release via β adrenoceptors. Parasympathetic nerve activity also increases secretion, whereas somatostatin, released from D cells adjacent to the glucagon-secreting A cells in the periphery of the islets, inhibits glucagon release. • Glucagon increases blood glucose and causes breakdown of fat and protein. It acts on specific G-protein-coupled receptors to stimulate adenylate cyclase, and consequently its actions are somewhat similar to β adrenoceptor-mediated actions of adrenaline. • Glucagon stimulates glycogen breakdown and gluconeogenesis, and inhibits glycogen synthesis and glucose oxidation.

Clinical uses of glucagon • Glucagon can be given intramuscularly or subcutaneously as well as intravenously. • Treatment of hypoglycaemia in unconscious patients (who cannot drink); unlike intravenous glucose, it can be administered by non-medical personnel (e.g. spouses or ambulance crew). It is useful if obtaining intravenous access is difficult. • Treatment of acute cardiac failure precipitated by βadrenoceptor antagonists. • Metabolic actions of glucogen on target tissues are thus the opposite of those of insulin. Glucagon increases the rate and force of contraction of the heart, although less markedly than adrenaline.