diabetes mellitus type i-kabera rene,md

8/3/2019 Diabetes Mellitus Type I-Kabera Rene,MD

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National University of Rwanda

Family and Community Medicine

Diabetes Mellitus Type I

KABERA Ren, MD

PGY IV Resident

Family and Community Medicine

National University of Rwanda


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Plan

Definition

Diagnosis criteria

Epidemiology

Pathophysiology

Prevention and treatment


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Definition

Diabetes mellitus encompasses a heterogeneous group of

disorders defined by a derangement in carbohydrate metabolismcaused by a defect in either insulin secretion or insulin action


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Diagnosis criteria Randomly measured plasma concentration of glucose of 200 mg/dL or

greater with classic signs and symptoms of diabetes (polyuria, polydipsia,

weight loss, fatigue) or

Fasting plasma concentration of glucose 126 mg/dL or greater with nocaloric intake for at least 8 hours previously or

Abnormal result of an oral glucose tolerance test (OGTT)[1.75 g/kg bymouth of anhydrous glucose dissolved in water (to a maximum of 75 g)]and plasma concentration of glucose after glucose load of 200 mg/dL or

Greater Any one of these criteria must be repeated on a subsequent dayto confirm the diagnosis, unless there is unequivocal hyperglycemia withacute metabolic decompensation (diabetic ketoacidosis).


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Epidemiology

The worldwide prevalence of DM has risen dramatically over

the past two decades, From an estimated 30 million cases in 1985 to 177 million in

2000

Based on current trends, >360 million individuals will havediabetes by the year 2030

The prevalence of type 2 DM is rising much more rapidly

Increasing obesity and reduced activity levels as countries

become more industrialized.


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DM I

The result of interactions of genetic, environmental, and

immunologic factors that ultimately lead to the destruction ofthe pancreatic beta cells and insulin deficiency.

Autoimmune process with linkage to particular HLA types.

Presence of autoantibodies directed against b cells Insulin deficient

autoantibody-positive insulin level and C-peptide decreased

Ketosis prone

Frequently younger than 18 yrs


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Pathophysiology

Other islet cell types [alpha cells (glucagon-producing), delta

cells (somatostatin-producing), or PP cells (pancreaticpolypeptide-producing)]

Functionally and embryologically similar to beta cells and

express most of the same proteins as beta cells,

Spared from the autoimmune process.

Pathologically, the pancreatic islets are infiltrated with

lymphocytes (in a process termed insulitis).

After all beta cells are destroyed, the inflammatory processabates, the islets become atrophic, and most immunologic

markers disappear


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PathophysiologyAbnormalities in the humoral and cellular arms of the immune system:

Islet cell autoantibodies;

Activated lymphocytes in the islets, peripancreatic lymph nodes, and

systemic circulation;

T lymphocytes that proliferate when stimulated with islet proteins; and

Release of cytokines within the insulitis. Beta cells seem to be particularly susceptible to the toxic effect of some

cytokines [tumor necrosis factor (TNF-), interferon , and interleukin 1 (IL-1)].

The islet destruction is mediated by T lymphocytes rather than islet

autoantibodies, as these antibodies do not generally react with the cellsurface of islet cells


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Pancreatic Hormones and Insulin

Receptor Agonists

The bulk of the pancreas is an exocrine gland secreting

pancreatic fluid into the duodenum after a meal. Inside the pancreas are millions of clusters of cells called islets

of Langerhans.

The islets are endocrine tissue containing four types of cells. In

order of abundance, they are: beta cells, which secrete insulin and amylin;

alpha cells, which secrete glucagon;

delta cells, which secrete somatostatin gamma cells, which secrete a polypeptide


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Pancreatic Hormones and Insulin

Receptor Agonists

Pancreatic Hormones

Insulin : Regular insulin ,Insulin analogs, Pre-mixed insulin

Amylin

Glucagon

Somatostatin

Pancreatic Polypeptide


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Insulin Insulin is an anabolic hormone.

Secretion of insulin in response to feeding governs use of glucose inperipheral tissues, such as muscle, through enhanced glucose uptakeand glycolysis.

Insulin facilitates energy storage in the forms of glycogen, fat, andprotein.

Adipogenesis is approximately 10 times more sensitive to theeffects of insulin than are the carbohydrate effects.

The effects on carbohydrate metabolism are the first manifestationof relative insulin deficiency

Hyperglycemia is caused by limited glucose uptake into cells and bydiminished insulin effects on the liver with increasedhepatic glucoseproduction from both breakdown of glycogen stores and increasedgluconeogenesis.


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Insulin


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Insulin


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Clinical presentation As serum level of glucose exceeds the renal threshold for

glucose reabsorption at approximately 180 mg/dL, Osmotic diuresis occurs, and the classic symptoms of polyuria

and compensatory polydipsia ensue.

The urinary symptoms may prompt evaluation for secondaryenuresis or for associated candidal diaper dermatitis or

vaginitis.


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Clinical presentation Fatigue and weakness are common from nocturia, disturbed

sleep, and breakdown of protein from muscle to provideamino acids as substrate for gluconeogenesis.

Polyphagia and weight loss also are common.

Visual disturbance can be caused by diffusion of glucose intothe lens and subsequent swelling.

Further elevation in serum level of glucose, and hence

osmolality, can cause lethargy


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Clinical presentation


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Management of KDA Confirm diagnosis (plasma glucose, positive serum ketones,

metabolic acidosis).

Admit to hospital; intensive-care setting may be necessary forfrequent monitoring or if pH < 7.00 or unconscious.

Assess:

Serum electrolytes (K+, Na+, Mg2+, Cl-, bicarbonate, phosphate)

Acid-base statuspH, HCO3-, PCO2, b-hydroxybutyrate Renal function (creatinine, urine output)

Replace fluids: 23 L of 0.9% saline over first 13 h (1015 mL/kgper hour); subsequently, 0.45% saline at 150300 mL/h; change to

5% glucose and 0.45% saline at 100200 mL/h when plasmaglucose reaches 250 mg/dL (14 mmol/L).


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Management DKA Administer short-acting insulin: IV (0.1 units/kg) or IM (0.3 units/kg),

then 0.1 units/kg per hour by continuous IV infusion; increase 2- to

3-fold if no response by 24 h. If initial serum potassium is < 3.3mmol/L (3.3 meq/L), do not administer insulin until the potassium iscorrected to > 3.3 mmol/L

Assess patient: What precipitated the episode (noncompliance,infection, trauma, infarction, cocaine)? Initiate appropriate workupfor precipitating event (cultures, CXR, ECG).

Measure capillary glucose every 12 h; measure electrolytes(especially K+, bicarbonate, phosphate) and anion gap every 4 hfor first 24 h.

Monitor blood pressure, pulse, respirations, mental status, fluidintake and output every 14 h.


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Management of KDA Replace K+: 10 meq/h when plasma K+ < 5.5 meq/L, ECG

normal, urine flow and normal creatinine documented;administer 4080 meq/h when plasma K+ < 3.5 meq/L or if

bicarbonate is given.

Continue above until patient is stable, glucose goal is 150

250 mg/dL, and acidosis is resolved. Insulin infusion may be

decreased to 0.050.1 units/kg per hour.

Administer intermediate or long-acting insulin as soon as

patient is eating. Allow for overlap in insulin infusion andsubcutaneous insulin injection


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Prevention and Treatment Prevention of Type 1 DM

A number of interventions have successfully delayed or preventeddiabetes in animal models.

Though results in animal models are promising, these interventions have not

been successful in preventing type 1 DM in humans.

The Diabetes Prevention Trialtype 1 concluded that administering insulin(IV or PO) to individuals at high risk for developing type 1 DM did not

prevent type 1 DM.

In patients with new-onset type 1 diabetes, treatment with anti-CD3

monoclonal antibodies has recently been shown to slow the decline in C-

peptide levels


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Management DM I Insulatard 2x/d: This is the simplest of the insulin regimens.

While it may help with the control of basal glycemia, it doesnot cover the meal time rise in glucose.

For many patients with diabetes type 2, this will be enough to

achieve glycemic control.

A good starting dose is 0.8 1.0 units/kg/day (type 1) or

0.3 0.6 units/kg/day (type 2),

Divided between a morning (60%) and evening dose (40%).

Injections should be given around 7 am and 7 pm.


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Management DM I Mixte 2x/d: Another regimen that requires only 2 injections

per day.

In some cases, it better controls meal time hyperglycemia,particularly in Rwandans, since the diet is high incarbohydrates. However, lunch is still not covered.

Also, for some patients, the fixed ratio of 70/30 will nothave enough regular insulin (patients may require a ratiocloser to 50/50).

Starting at a dose of 0.3 0.6 units/kg/day, dividedbetween a morning and evening dose, is reasonable.

Injection should be given 20 30 minutes before breakfastand 20 30 minutes before dinner.


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Management DM I Insulin Lente/Rapide 2x/day: For patients who need to have

the individual doses of lente and rapide adjusted (instead ofthe fixed ratio of insulin mixte 70/30), this regimen may work

better.

The patient must mix insulin from two vials (lente and rapide)

and give the injection 2x/day (at 7 am and 7 pm).

The morning or evening doses of lente or rapide can be

individually adjusted. Mid-day hyperglycemia can be

controlled with the morning dose of lente.


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Chronic Complications of Diabetes

Mellitus

Microvascular

Eye disease

Retinopathy (nonproliferative/proliferative)

Macular edema

Neuropathy

Sensory and motor (mono- and polyneuropathy)

Autonomic Nephropathy


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Chronic complicationsMacrovascular

Coronary artery disease Peripheral arterial disease

Cerebrovascular disease


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Chronic complicationsOther

Gastrointestinal (gastroparesis, diarrhea) Genitourinary (uropathy/sexual dysfunction)

Dermatologic

Infectious

Cataracts

Glaucoma

Periodontal disease


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References Harrison's Principles of Internal Medicine

Chronic Care Integration for Endemic Non-CommunicableDiseases ,Rwanda edition: cardiac, renal, diabetes,

pulmonary, and palliative care(paterner in ealt

Rudolph's Pediatrics


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End

Thank you

diabetes mellitus type i-kabera rene,md

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