Diabetes Melitus dan Komplikasinya.

Jossep Frederick William,dr.

Diabetes.

Natural History of Type 1 Diabetes

PUTATIVE ENVIRONMENTAL TRIGGER
CELLULAR (T CELL) AUTOIMMUNITY
HUMORAL AUTOANTIBODIES

BETA CELL MASS

(ICA, IAA, Anti-GAD65, IA2Ab, etc)

LOSS OF FIRST PHASE INSULIN RESPONSE

(IVGTT)

GENETIC PREDISPOSI TION

INSULITIS BETA CELL INJURY

GLUCOSE INTOLERANCE
(OGTT)

PRE-

CLINICAL ONSET
DIABETES

DIABETES

TIME

Symptoms of diabetes

Polyuria (Sering kencing) Polydipsia (Sering merasa haus) Penurunan Berat Badan.

Gejala lainnya dari Diabetes.

Rasa lapar. Letih. Kulit yang kering. Mudah terkena infeksi. Feet ulceration Hilangnya sensasi di kaki. Erectile dysfunction.

Diagnosing Diabetes
Fasting Blood Glucose (FBG):
Blood Glucose Level is measured after a fast

Oral Glucose Tolerance Test (OGTT)

Blood glucose level is measured fasting and two hours after drinking a glucose-rich beverage

Diagnosis Pre-Diabetes Diabetes

FBG 100-125 126

OGTT 140-199 200

From http:// www.diabetes.org

Pathophysiology of Type 2 Diabetes

Insulin resistance.
Beta cell dysfunction.

Pathophysiology of Type 2 Diabetes Insulin Resistance

Insulin Resistance pada saat awal dari penyakit.
Insulin resistance saja tidak akan menghasilkan seseorang terkena diabetes. Bila fungsi dari beta sell norma, maka orang tersebut akan dapat mengkompensasikan terjadinya insulin resistansi dengan meningkatkan produksi dari insulin.

Pathophysiology of Type 2 Diabetes Beta cell defect

Semua penderita diabetes tipe 2 setidaknya akan mengalami defek baik dalam fungsi dari beta sel dan juga jumlah dari beta sel yang berfungsi dalam pancreas. Function: in the (UKPDS), newly diagnosed people with diabetes had, on average, only about 50% of normal beta-cell function.[Diabetes. 1995;44:1249-1258 , Diab Res
Clin Pract. 1998;40(suppl):S21-S25.]

Mass: Autopsy studies comparing the volume of beta cells in nondiabetic individuals with that of people with diabetes found a 41% decrease in beta-cell mass among people with type 2 diabetes

Pathophysiology of Type 2 Diabetes Beta cell defect IV glucose infusion to a nondiabetic individual results in a biphasic insulin response: - Immediate first-phase insulin response in the first few minutes. - Second-phase response, more prolonged.

Pathophysiology of Type 2 Diabetes Beta cell defect This first-phase insulin response is absent in type 2 diabetic patients contributing to the excessive and prolonged glucose rise after a meal in those with diabetes Diabetologia. 2004;47(suppl 1):A279. Infusing insulin can only partially improve this condition.

Pathophysiology of Type 2 Diabetes Other Factors

Historically, hyperglycemia in diabetes has been viewed as a failure of insulin-mediated glucose disposal into muscle and adipose tissue. This looks to be an over simplification of a more complicated issue.

Progres dari Diabetes.

Normal

IGT
Primary prevention

Type 2 DM
Secondary prevention

Komplikasi

Kecacatan Dan Kematian

Tertiary prevention

Pengendalian terjadinya komplikasi dan

penanganan kerusakkan yang terjadi. Pencegahan terjadinya komplikasi dari diabetes. Pencegahan terjadinya diabetes pada mereka yang memiliki resiko tinggi.

Diabetes: Komplikasi.
Macrovascular
Stroke

Microvascular
Diabetic eye disease (retinopathy and cataracts)

Heart disease and hypertension 2-4 X increased risk Renal disease Peripheral vascular disease

Erectile Dysfunction

Peripheral Neuropathy Foot problems

Meltzer et al. CMAJ 1998;20(Suppl 8):S1-S29.

Nephropathy Diabeticum.

Peripheral arterial disease.

Diabetic Neuropathy.

The Good News

By managing the ABCs of diabetes, people with diabetes can reduce their risk for heart disease and stroke.

A stands for A1C B stands for Blood pressure C stands for Cholesterol PLUS More Bs
BMI Blood Sugars

Body Mass Index

Being overweight or obese is a leading risk factor for type 2 diabetes. A healthy weight is measured by your body mass index (BMI).

BMI Below 18.5 18.5-24.9 25-29.9 Over 30

Category Underweight Healthy Overweight Obese

BMI Goal = less than 25

Memonitor kadar gula darah.

Tempat kerja dari berbagai macam obat diabetes.

LIVER PANCREAS GLUCOSE PRODUCTION Metformin Thiazolidinediones INSULIN SECRETION Sulfonylureas: Glyburide, Gliclazide, Glimepiride INTESTINE Non-SU Secretagogues: Repaglinide, Nateglinide GLUCOSE ABSORPTION Alpha-glucosidase inhibitors ADIPOSE TISSUE MUSCLE

PERIPHERAL GLUCOSE UPTAKE

Thiazolidinediones Metformin

Hypoglycemia

Wt. Gain

Edema

GI effects

Lactic Acidosis

Liver Toxicity

Use in Renal Failure

Glyburide Gliclazide

4+ 2+ +

+ 0

0 0

Glimepiride
Repaglinide Nateglinide Metformin Acarbose Rosiglitazone Pioglitazone

2+
1+ 1+ 0 0 0 0

+
+ ? 0 0 + +

0
0 0 0 0 + +

0 0 2+ 3+ 0 0

0
0 0 + 0 0 0

0 0 0 * *

+
+ +
+

* Liver

enzyme monitoring recommended in product monographs

Adapted from Lebovitz H: Endocrinol & Metab Clinics of NA; 30 (4)909-933

Drug
Glyburide

Trade
Diabeta

Dose
Start 1.25-5 mg od Spit dose bid > 10mg/d Max 10 mg bid Start 80 mg bid Max 160 mg bid Start 30 mg od Max 120 mg od Start 1-2 mg od Max 8 mg od Start 0.5 mg tid-qid Max 4 mg qid Start 60-120 mg tid Max 180 mg tid Start 500 mg od-bid Max 1000 mg bid Start 15-30 mg od Max 45 mg od Start 4 mg od Max 4 mg bid

Cost
$14/mos

ODB
Yes

Gliclazide Gliclazide MR Glimepiride Repaglinide Nateglinide Metformin Pioglitazone Rosiglitazone

Diamicron Diamicron MR Amaryl Gluconorm Starlix Glucophage Actos Avandia

$90/mos $30/mos $30-40/mos $45/mos $45/mos $14/mos $92/mos $ 60/mos $ 120/mos

No Exp Sect 8 No Exp Sect 8 No Yes Exp Sect 8 Exp Sect 8

Prinsip kerja Sulfonil Urea

Prinsip kerja Metformin.

Summary of available insulin preparations

Glucose lowering Basal Agent NPH Type / Administration Intermediate-acting human Once or twice daily at bedtime breakfast Long-acting analogue Once or twice daily at bedtime breakfast Long-acting analogue Once daily at bedtime or before breakfast Human or analogue mix Twice daily before breakfast and dinner Fast-acting human Before meals Rapid-acting analogue Before meals Rapid-acting human Before meals Postmeal

Detemir

Glargine

Premixed Regular Aspart, glulisine, lispro Inhaled insulin

Penggunaan Pen Insulin

Evidence-based guidelinederived treatment algorithm

Diagnosis Lifestyle intervention then metformin
HbA1c 6.5 %

Add sulfonylurea
HbA1c 6.5 % HbA1c 6.5 %

*Alternatively, start thiazolidinedione before sulfonylurea, and sulfonylurea later.

Add thiazolidinedione*
HbA1c 7.5 %

Add insulin
HbA1c 7.0 %

Start insulin

intensify insulin

Meal-time + basal insulin + metformin thiazolidinedione

IDF. Global Guideline for Type 2 Diabetes. 2005

DM
GHS

Tahap I

Tahap II

Tahap III

GHS + Monoterapi
Catatan : 1. GHS = Gaya Hidup Sehat 2. Dinyatakan gagal bila terapi selama 2 -3 bulan pada tiap tahap tidak mencapai target terapi HbA1C < 7 % 3. Bila tidak ada pemeriksaan HbA1C dapat dipergunakan pemeriksaan glukosa darah rata2 hasil pemeriksaan beberapa kali glukosa darah sehari yang dikoversikan ke HbA1C menurut kriteria ADA, 2010

GHS + Kombinasi 2 OHO

Jalur Pilihan Alternatif, bila : -Tidak terdapat insulin -Diabetisi betul-betul menolak insulin -Kendali Glukosa belum Optimal

GHS + Kombinasi 2 OHO + Basal Insulin

GHS + Kombinasi 3 OHO

Insulin Intensif

Kadar HbA1C
<7%
GHS
Gaya Hidup

7-8 %
GHS + Monoterapi Met, SU, AGI, Glinid, TZD, DPP-IV

8-9 %

>9 %

9-10 %

>10 %

Sehat

Penurunan Berat badan Mengatur diit latihan jasmani teratur

GHS + Kombinasi 2 Obat Met, SU, AGI, Glinid, TZD, DPP-

GHS + Kombinasi 3 Obat Met, SU, AGI, Glinid, TZD, DPP-IV

IV
Catatan : 1. Dinyatakan gagal bila dengan terapi 2-3 bulan tidak mencapai target HbA1C <7% 2. Bila tidak ada pemeriksaan HbA1C dapat digunakan pemeriksaan glukosa darah. Rata2 glukosa darah sehari dikonversikan ke HbA1C menurut kriteria ADA 2010

GHS + Kombinasi 2 Obat Met, SU, AGI, Glinid, TZD + Basal Insulin

GHS + Insulin Intensif

Efek samping dari TZD

Edema
4-5% of patients get mild-moderate edema 15% if TZD used in combo with insulin

Mild anemia (dilutional) Weight gain

Increase in subcutaneous not visceral fat

Myalgia (pioglitazone only)

Myalgia 5.4% pioglitaz. versus 2.7% placebo Few patients with unexplained CK > 10x ULN

Contraindicated in class II, III and IV CHF Contraindicated if ALT > 2.5x ULN or active liver disease

TZDs: effect on Metabolic Syndrome

Reduce insulin resistance/blood sugar Mild decrease in diastolic BP (2-4 mmHg) Lipids:
TG HDL (pioglitazone > rosiglitazone?) LDL (pioglitazone) LDL (rosiglitazone)
No change in ApoB so due to larger less atherogenic particle size

Decrease in carotid artery intimal-media thickness (IMT)

Bagaimana kita memberikan insulin kepada mereka yang terkena diabetes tipe 2 ?

Algorithm driven dose titration basal regimen*

Once daily intermediate or long-acting insulin Begin 10 U or 0.2 U/kg, titrate by 2 U every 3 days using pre-breakfast plasma glucose (PG) until in target range (100 110 mg%)

HbA1c 7.0% after 3 months Check pre- breakfast, lunch, dinner, and bedtime PG Add rapid-acting insulin to the meal with the highest excursion Begin 4 U and adjust by 2 U every 3 days based on PG change

Add additional meal-time injections if HbA1c 7.0% after 3 months

*Insulin regimens should be designed taking lifestyle and meal schedule into account; this algorithm provides a basic guideline for initiation and adjustment of insulin. Regimens with onceor twice-daily premixed insulins are also possible.
Inhaled

insulin dosing in 1 mg ( 3 U) steps.

Nathan DM et al. Diabetes Care. 2006;29:1963-1972

Basal-bolus insulin treatment: matching insulin administration to insulin needs

Rapid-acting insulins

100

B
80

Basal insulins

U/ml

60 40 20

Normal pattern

0600

0800

1200

1800

2400

0600

Time of day
B = breakfast; L = lunch; D = dinner
Riddle MC. CADRE Core Slide Kit. 2003 Polonsky KS et al. N Engl J Med. 1988;318:1231-1239

Dosing of dry powder inhaled insulin

Dose Dose of Regular SC Insulin
3U 6U 8U 11 U

1-mg Blisters per Dose

1 2 1

3-mg Blisters per Dose

1 1

1 mg 2 mg 3 mg 4 mg

5 mg
6 mg

14 U
16 U

1
2

Exubera (insulin human [rDNA origin]) inhalation powder [prescribing information]. New York: Pfizer Inc; 2006

Tipe dari insulin.

Diagnosis dari Metabolik Syndrome. Terdapat 3 hal dibawah ini: Abdominal obesity (M > 102 cm, F > 88 cm) TG > 200mg% Low HDL (M < 45mg%, F < 50mg%) BP > 130/85 FPG > 120 mgr%/dl

H y p e r g l y c e m i a

Terjadi karena gula darah yang tinggi dengan sel dalam tubuh mengalami kekurangan glukosa. Menyebabkan terjadinya dehidrasi yang serius. Saat kadar gula dalam sel tubuh terus menurun tubuh akan mulai menghasilkan keton dan produksi dari asam akan meningkat. Biasanya terjadi pada kadar gula darah 180mg/dl yang terjadi selama 3 hari terus menerus atau 240mg/dl

H y Penyebab : p Pasien lupa menggunakan insulin. e Pasien makan berlebihan, membebani tubuh dengan karbohidrat. r Pasien mengalami infeksi yang menganggu g keseimbangan insulin dan glukosa. l y c e m i a

H y Signs and Symptoms p Polyuria (frequent urination) e Polydypsia (excessive thirst) r Polyphagia (excessive hunger) g Nausea/Vomiting l Kussmauls Respiration's (Deep and Rapid) y Warm, Dry Skin c Fruity Odor on Breath e Abdominal Pain m i a

H y Signs and Symptoms Cont.. p Falling Blood Pressure e Fever r Decreased LOC g l y c e m i a

H y Treatment BLS p Airway e Breathing r Circulation g Disability l Asses for trauma:protect C-spine if indicated y Administer O2 per Pt assessment c Suction airway if needed e m i a

H y Treatment BLS p Obtain Hx if possible e Check finger stick r Protect airway g Call for ALS if Available (dont delay transport) l Transport y c e m i a

Comparison
Hypoglycemia
Onset Sudden Skin cold, pale, moist Normal Weak, rapid pulse Weakness/ uncoordination Headache Irritable/Nervous Behavior

Hyperglycemia
Slower onset Skin warm, red, dry Acidic Breath
Kussmaul Respiration's

Rapid Pulse Polyuria, polydypsia, polyphagia Nausea/Vomiting Falling Blood Pressure

supplemental regular insulin scale

Preprandial glucose mg/dl <100 100-140 140-160 Additional units (regular insulin) 0 2 3

160-180
180-200 200-250 250-300 >300

4
5 6 8 10

NUTRITION RECOMMENDATION FOR PERSONS WITH DIABETES

CATEGORY Weight management Carbohydrate(% of energy) Polysaccharides Monosaccharides and discharides Glycemic index Fiber, total

RECOMMENDATIONS
Attain & maintain desirable body weight (BMI25)

55-65%
Emphasixe whole grains, legumes, vegetables Use in moderation Incorporate into exchanges and teaching material 25-50 g/d (15-25 g/1000 kcal)

Nutrition Recommendation for Persons with Diabetes

Nutrient Carbohydrate, % of kcal Proteins, % Fat, total, % Saturated, % Monounsaturated% Polyunsaturated % Cholesterol, Fiber, g/day Sodium, mg/day Alcohol ADA about 50% 10-20% 30%d <10% 10-20%` <10% <300 mg/day 20-35 g/day <2400 mg if hypertensive drinks/day HCF Nutrition Fdnb,c 50-60% 10-15% (0.8 g/kg) 30%e <10% 10-15% <10% <200 mg/day about 35 g/day (15-25 g/1000 kcal <1000 mg/1000 kcal Men 2 drinks/day Women 1 drink/day Multivitamin-mineral daily antioxidant supplements

Vitamin supplements

Not recommended

American Diabetes Association. Nutrition recommendations and principles for people with diabetes mellitus. JADA 1994;94-905 Anderson JW, Geil PB. Nutrition management of diabetes mellitus. In Shils M. Modern Nutrition in Health and Disease, 8th edition. Philadelphia: Lea & Febiger, 1994;1259-86. Anderson JW, Professional guide to high fiber fitness plan. Lexington, KY: HCF Nutrition Research Fdn. 1995;10.110.22 Individualization recommended. More fat permitted and less carbohydrate acceptable. Up to 35%of energy from fat can be used for nonobese individuals with acceptable serum triglyceride values if the additional fat comes from monounsaturated sources and saturated and polyunsaturated fats remain under 10% each.

Glycemic Index (GI) Ranking of Selected Starchy Foods Class I (Higher: GI >90) Class II Intermediate: GI = 7090 Oat bran Oatmeal Most cookies or cereals biscuits polished rice Whole-wheat bread Boiled Sweet corn Boiled new potatoes Yams Sweet potatoes Class III (Lower: GI <70)

Most breads Plain crackers Most breakfast Most potatoes Pancake & waffles Corn chips Most cakes

Pumpernickel bread Most pasta Boiled rice Most dried legumes Nuts Barley Dry beans & lentils

Glycemic response of nondiabetic individuals to 50 g carbohydrate from new potatoes or kidney beans. B. Glycemic response of healthy individuals to 50 www.themegallery.com g of glucose, sucrose, or fructose

Factors affecting the Glycemic Response to food

Rate of ingestion Food form Food components Fat content Fiber content Protein content Starch characteristic Methods of cooking and processing Physiologic effects Pregastric hydrolysis Gastric hydrolysis Gastric emptying rate Intestinal response Intestinal hydrolysis and absorption Pancreatic and gut hormone response Colonic effects

High Fiber Intakes Advantages and Disadvantages

Advantages Slow nutrition digestion and absorption Decrease postprandial plasma glucose Increase tissue insulin sensitivity Stimulate glucose use Attenuate hepatic glucose output Decrease counterregulatory hormone release (e.g.,glucagon) Lower serum cholesterol Lower fasting and postprandial serum triglycerides May attenuate hepatic cholesterol synthesis May increase satiety between meals Disadvantages Increase intestinal gas Temporarily may cause abdominal discomfort or gastrointestinal distress May alter pharmacokinetics of mineral absorption and certain drugs

 FREQUENCY:
Start slow, increase slow 3 times : breakfast, lunch and dinner 2 3 times snack (low calorie/low GI: fruits)

With low/moderate physical activity

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TEE for hypermetabolism

TEE = BEE x TEF x PA x SF

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 Use ideal body weight for underweight patient Use adjusted body weight for overweight patient Ideal body weight = ((Body height cm)-100) (10%x (Body height-100)) Adjusted body weight = Actual body weight (ABW) (25% x (Actual Body Weight- Ideal Body Weight))

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Thermogenic Effect of Food

TEF is the amount of energy used for digestion, absorption and utilization of food consumed. - SDA of protein 30% BEE - SDA of carbohydrate < protein - SDA of fat the lowest
The average of TEF: 10%
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Physical Activity (PA)

PA very light PA light PA moderate PA heavy PA very heavy

= 10-30% BEE = 30-50% BEE = 50-80% BEE = 80-100% BEE = > 100% BEE

Bedridden 10% BEE Ambulatory 20% BEE

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Stress Factor (SF) Postoperative (without comp.) Fracture of long bone Cancer Peritonitis/sepsis Serious infection/mult. Trauma Multiple organ failure syndr. Burn

1.00-1.10 1.15-1.30 1.10-1.30 1.10-1.30 1.20-1.40 1.20-1.40 1.20-2.00

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PROTEIN REQUIREMENT: Underweight/normoweight: based on actual bodyweight Overweight/obese: based on adjusted body weight With normal renal function: 0,8 1 g/ kgBW

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LIPID REQUIREMENT: < 30% TEE non protein SFA/trans fatty acid: < 10% TEE non protein MUFA : 10-12% TEE non protein PUFA: 10% TEE non protein Cholesterol < 200 mg/day
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