Pdf Diabetes for nurses

DIABETES MELLITUS

IN RENAL COMPLICATIONS

นพ.กมล โฆษิตรังสิกุล

อายุรแพทย์โรคไต

โรงพยาบาลมหาราชนครศรีธรรมราช

WHAT IS DIABETES ?

A chronic metabolic disorder causing elevation of blood glucose and specific & nonspecific complications

INTRODUCTION

Between 1985 and 2010, the worldwide prevalence of DM has risen almost 10-fold, from 30 million to 285 million cases.

In the United States, DM prevalence in 2010 is estimated at 26 million, or 8.4% of the population.

A significant portion of persons with DM are undiagnosed.

THE BURDEN OF DM IN THAILAND

Prevalence of DM in Thai adults (age > 35 years) was 9.6%

4.8% Known DM, 4.8% newly Dx DM

2.4 million people have diabetes

Fair access to diabetes medications

Diabetes Care 2003; 26: 2758-63

INCIDENT COUNTS & ADJUSTED RATES OF ESRD

2012 USRDS annual Data Report

CAUSE OF CKD IN THAI RRT 2003

DM, 1348, 34%

HT, 1043, 26% CGN, 558,

14%

Other, 448, 11%

Unknown, 613, 15%

DIAGNOSIS OF DM

Criteria for the diagnosis of DM include one of the following:"

Hemoglobin A1c >6.5%

Fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL)

Symptoms of diabetes plus a random blood glucose concentration ≥11.1 mmol/L (≥200 mg/dL)

2-h plasma glucose ≥11.1 mmol/L (≥200 mg/dL) during a 75-g oral glucose tolerance test.

ADA 2010

DIAGNOSIS

Categories of increased risk for DM"

Impaired fasting glucose (IFG) for a fasting plasma glucose level of 5.6–6.9 mmol/L (100–125 mg/dL)

Impaired glucose tolerance (IGT) for plasma glucose levels of 7.8–11.1 mmol/L (140–199 mg/dL) 2 h after a 75-g oral glucose load

HbA1C 5.7-6.4%

การแปลผล FPG

Normal FG IFG Provisional DM

100 126 mg/dL

OGTT

การทดสอบความทนกลูโคส

เป็นวิธีทดสอบการทํางานของβ-cell ของตับอ่อน ในการหลั่ง

insulin หลังกินกลูโคสในปริมาณสูง (75 g)

คนปกติสามารถลดระดับนํ้าตาลลงมาได้ภายใน เวลา 2 ชั่วโมง

ผู้ที่มีการหลั่งinsulin บกพร่องหรือเป็นโรค เบาหวาน จะต้องใช้เวลาในการลดระดับนํ้าตาลนานกว่า 2 ชั่วโมง

75 gm glucose

ข้อบ่งชี้ การส่งตรวจ OGTT

1. เพื่อตรวจยืนยันการวินิจฉัยโรคเบาหวานในกรณีที่การตรวจ FPG ให้ผลไม่ชัดเจน(IFG)

2. FPG ให้ผลปกติแต่มีความสงสัยว่าจะเป็นโรคเช่น

2.1 มีอาการทางคลินิกของโรคเบาหวาน เช่น retinopathy,

neuropathy, peripheral arterial disease

2.2 กลุ่มที่มีแนวโน้มอาจจะเป็นโรคเบาหวานได้ มากกว่าผู้อื่น (high

risk group)

การแปลผล OGTT

Normal GT Provisional DM

140 200 mg/dL

75 gm glucose then 2 hour plasma glucose

Impaired GT

(DIABETES CARE 2007; 30)

!

SCREENING

Screening with a fasting plasma glucose level is recommended every 3 years for individuals over the age of 45, as well as for younger individuals who are overweight (body mass index ≥25 kg/m2) and have one or more additional risk factors.

ADDITIONAL RISK FACTORS

Physical inactivity

First-degree relatives with diabetes

Members of high-risk ethnic population(eg. African American, Latino, Native American, Asian American, Pacific Islander)

Women who delivered a body weighing 9 Ib (4 kg) or were diagnosed with GDM

Hypertension (140/90 mHg or on therapy for hypertension)

ADDITIONAL RISK FACTORS

HDL < 35 mg/dL and/or a triglyceride level > 250 mg/dL

Women with polycystic ovary syndrome

A1C 5.7 %, IGT, IFG on previous testing

Other clinical conditions associated with insulin resistance (eg. severe obesity, acanthuses nigricans)

History of CVD

ADA CLASSIFICATION OF DIABETES

Type 1 Diabetes Mellitus

Type 2 Diabetes Mellitus

Other specific types

Gestational Diabetes Mellitus

DIABETES MELLITUS

Type 1 Diabetes (5-10%)

Juvenile Onset, IDDM, type I

Auto-immune disease

Pancrease is unable to produce insulin (Beta cell destruction)

Required insulin for survival

Generally diagnosed from birth to age 30, highest incidence age 12-18

DIABETES MELLITUS

Type 2 Diabetes (90-95%)

Adult onset, NIDDM, type II

Variable degree of insulin deficiency coupled with insulin resistance

Disorder associated with obesity and the ageing process

Generally diagnosed after age 40

DIABETES MELLITUS

Gestational Diabetes Mellitus (GDM)

Hyperglycemia first diagnosed in pregnancy

Diagnosis made by OGTT

DIABETES MELLITUS

Other specific types

Maturity-Onset Diabetes of the Young (MODY)(<1%)

Pancreatic disease

Drug

etc.

ETIOLOGY OF DIABETES

Adapted from DeFronzo RA.Diabets 1988;37:667-87

COMPLICATION OF DIABETES

Acute complication: Hyperglycemic crisis

Diabetic Keto-Acidosis (DKA)

Hyperglycemic Hyperosmolar State (HHS)

Long term complications

Microvascular

Macrovascular

ACUTE COMPLICATION

Type I DM DKA

Rapid deep breathing Abdominal pain

Nuasea/Vomiting Fruity odor of ketone

Type 2 DM HHS

Weight loss Seizure

Polyuria Polydipsia

Drowsy Coma

ACUTE COMPLICATION

DKA HHS

DM Type1 Type2

Glucose(mg/dl) >250 >600

pH <7.3 >7.3

Serum HCO3(mEq/L) <15 >20

BUN (mg/dl) <25 >30

S. Osmolality <320 >320

Ketones > 3+ - / small

CHRONIC COMPLICATIONS OF DM

Ophthalmologic: nonproliferative or proliferative diabetic retinopathy, macular edema, rubeosis of iris, glaucoma, cataracts

Neurologic: distal symmetric polyneuropathy, polyradiculopathy, mono-neuropathy, autonomic neuropathy

CHRONIC COMPLICATIONS OF DM

Gastrointestinal: gastroparesis, diarrhea, constipation

Genitourinary: cystopathy, erectile dysfunction, female sexual dysfunction, vaginal candidiasis

CHRONIC COMPLICATIONS OF DM

Cardiovascular: coronary artery disease, congestive heart failure, peripheral vascular disease, stroke

Lower extremity: foot deformity (hammer toe, claw toe, Charcot foot), ulceration, amputation

Dental: Periodontal disease

CHRONIC COMPLICATIONS OF DM

Dermatologic: Infections (folliculitis, furunculosis, cellulitis), necrobiosis, poor healing, ulcers, gangrene

CHRONIC COMPLICATIONS OF DM

Renal: proteinuria, end-stage renal disease (ESRD), type IV renal tubular acidosis

CHRONIC COMPLICATIONS

cataract retinopathy

!!

proteinuria !!

neuropathy !!!

Arthero sclerosis

!Blindness!!!

Kidney failure !!Amputation!! MI!!Stroke !

CAUSES OF MORTALITY IN DIABETES

32 !

Heart Disease

Cerebrovascular Disease

Other Pneumonia/ Influenza Malignant

Neoplasms

Diabetes

Geiss LS, et al. In: Diabetes in America. 2nd ed. NIH Publication No. 95-1468. 1995:233-257.

Causes of Mortality in Patients With Diabetes

10% 13%

13% 4% 5%

55%

Geiss LS, et al :Diabetes in America 2 nd ed, NIH publication No.95-1468. 1995:233-257

CLINICAL PROGRESSION

Stage Onset Designation Kidney change

1 เมื่อวินิจฉัย Hyperfunction GFR ↑

2 2-3 ปี Silent stage GFR ↑ , Thick GBM

3 >5 ปี Incipient stage GRF ↑ or ↔

Microalbuminuria

4 >10 ปี Overt DN GFR ↔ or ↓

Clinical proteinuria

5 >15 ปี ESRD GFR  < 10 ml/min

DEFINITION IN ALBUMIN EXCRETION

.

Random** 24 hr Urine Timed (microgram/min)

Normal <30 mg/g <30 mg/24h <20 Microalbuminuria 30-300 mg/g 30-300 mg/24h 20-200 Macroalbuminuria >300 mg/g >300 mg/24h >200

Diabetes Care 28, Supple 1, Jan 1998

No nephropathy

Microalbuminuria

Macroalbuminuria

Rising Cr, RRT

0.3%

2.8% 0.1%

0.1%

1.4%/ years

2.3%

3.0%

19.2%

2.0% / years

4.6%

DEAT

H

UKPDS 64: Kidney Int 2003; 63:225-232

GLYCEMIC GOAL IN ADULT

GLYCEMIC GOAL IN ADULT

DIABETES(CARE,(VOLUME(35,(SUPPLEMENT(1,(JANUARY(2012!

Monotherapy

Insulin therapy

Combination oral therapy

Lifestyle modification

Expected HbA1c (time allotted)

�1% (3 months)

�1 to 2% (1�3 months)

�1 to 2% fall per additional OHA (1�3 months)

Unlimited

T2DM treatment strategies

Adapted from Bergenstal RM. In: De Fronzo RA, et al (eds). International Textbook of Diabetes Mellitus. 3rd ed. Chichester, New York: John Wiley & Sons; 2004:995�1015.

PRIMARY SITE OF ACTION

48 !

Glucose

Adipose tissue

Gut

Stomach

Liver

Sulphonylureas and glinides

TZDs

Biguanides

Muscle

Pancreas Insulin

Adapted from Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl 1): S32–40; Nattrass M et al. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13: 309–29.

α-glucosidase inhibitors

Primary sites of action of oral antidiabetic agents

incretin

METFORMIN

Decrease hepatic glucose production

Mechanism: Unclear, Activating the AMP-activated protein kinase (AMPK)

METFORMIN

J. Clin. Invest. 2001;108(8): 1167-74.

CLINICAL ADVANTAGES OF METFORMIN

1.Does not cause weight gain

2.Does not cause hypoglycaemia

3.Improve lipid profile

Decrease plasma triglyceride 10-20%

Decrease plasma cholesterol 5-10%

Small increases in HDL-C Levels

4.Decrease plasma insulin levels

ADVERSE EFFECTS OF METFORMIN

1.Gastrointestinal 10-30%

diarrhea, nausea, abdominal discomfort

anorexia, metalic taste

2.Impaired absorption of Vit B12 and folate

3.Lactic acidosis

CONTRAINDICATION & CAUTION FOR THE USE OF METFORMIN

Renal impairment :

Cr > 1.5 mg/dL ; men

Cr >1.4 mg/dL ; women

Cardiac or respiratory insuffiency

History of lactic acidosis

Severe infection

Liver disease

Alcohol abuse

Use of intravenous radio contrast agents

METFORMIN USE BASED ON GFR

DIABETES CARE, VOLUME 34, JUNE 2011

SULFONYL UREA

Pancreatic action

Stimulation of insulin secretion by closing ATP-dependent potassium channels causing calcium influx

INSULIN SECRETAGOGUES

Drug ! Dose !T 1/2 !Metabolites !Excretion"! ! !(mg/d) ! (h)"

Chlorpropamide 100 - 500 36 Active or Kidney

unchanged

Glipizide 2.5 - 30 2-4 Inactive Kidney 80%

Bile 20 %

Gliburide 1.25 - 20 10 Inactive & Kidney 50%

weakly active Bile 50 %

Glimepiride 1 - 8 9 Inactive & Kidney 60%

weakly active Bile 40 %

Repaglinide 1.5 - 6 1 Inactive Bile

CONTRAINDICATION TO SULFONYL UREA

1. IDDM

2. post-pancreatectomy

3.During acute diabetic complication

4.During stress, infection or major operation

5.Renal impairment

6.During gestation?

7.Adverse drug reaction

HYPOGLYCAEMIA FROM SULFONYLUREAS

Risk factors

1.Age > 70 yr

2.Poor nutrition

3.Alcohol intake

4.Impaired renal function

5.Drug interactions

THIAZOLIDINE DIONE

Ligand for PPAR ɣ , a nuclear receptor transcription factor regulates many gene expression involved in CHO and lipid metabolism

Specific mechanism: unclear

⬆️ insulin-mediated glucose uptake by skeleton muscle

⬇️ lipolysis and enhance adipocyte differentiation

indirect effect mediated through adipokines

ADVERSE EVENT OF TZD

1.Edema: generally dose related, more commonly observed when combination with SU, Insulin

2.Weight gain: up to 8 kg

3.Anemia: Hct drop around 3%

4.Congestive heart failure

5.Macular edema

6.Bone fractures

7.Exacerbate Grave’s opthalmopathy

INSULIN

Types Examples

Bolus (Meal) Insulin Rapid-acting lispro, aspart, glulisine Short-acting Regular

Basal (Background) Insulin Intermediate-acting NPH, Lente Long-acting Glargine

Pre-Mixed Insulin NPH/Regular 70/30, 50/50 NPL/Lispro Mix 75/25 NPA/Aspart Mix 70/30

INSULIN ACTION

76 !

Insulin Action: Comparison of New Insulin Analogs

0

20

40

60

80

100

120

140

0 2 4 6 8 10 12 14 16

Regular

Rapid (Lispro, Aspart)

Insu

lin L

evel

(µU

/ml)

Hours

Intermediate (NPH)

Long ( Detemir,Glargine)

INSULIN ACTIONComparison of Human insulins and insulin analogues

Insulin Onset of Duration of

Preparations Action Peak Action Action

Lispro/Aspart 5-15 min 1-2 hr 4-6 hr

Human Regular 30-60 min 2-4 hr 6-10 hr

Human NPH/Lente 1-2 hr 4-8 hr 10-20 hr

Glargine/Detrimir 1-2 hr Flat ~24 hr

Endocrinol Metab Clin North Am 2001;30:944

Dyslipidemia

DM#Type#II#&#CVD,#CKD,#CVD#with#age#>#40#yr##

with#TOD##or#>#1#risk##

##

LDL>C#goal#<#70#mg/dl !Non#HDL>C#<100#mg/dl##

#Apo#B#<#80#mg/dl#

!!

!All!DM!type!II!!patients!

!LDL0C<100!mg/dl!

Non!HDL0C!<130!mg/dl!!!Apo!B!<!100!mg/dl!

!

European)Heart)Journal)(2011))32,)1769–1818)

!Mod!to!severe!CKD!

LDL.C!target!70!mg/dl!!

Expert!:!Sta;n!may!slow!rate!of!kidney!func;on!loss!

!

CKD$=$CAD$Risk$equivalent$$

LDL4C$lowering$is$useful$$

European)Heart)Journal)(2011))32,)1769–1818)

FOLLOW UP AFTER START ACEI/ARB