May 19,2013*

A 44 year-old male, Mr. Huang presents to your clinic with weight loss 10 kg (8575 kg) in 1 monthThe associated symptoms are polyuria and polydipsiaHis major medical history is unremarkableHe has no travel history in recent 3 monthsHe Smokes tobacco 1 pack/day for 20 yearsHe drinks Taiwan beer a bottle/day (4.5% alcohol, 600ml)No family history of cardiovascular disease*

Vital sign: BT 36.3, RR 18/min, HR 92 beat/min, BP 139/91 mm HgBody height 171 cm, weight 75 kg (85 kg, 1 month ago), BMI 25.6 (29.1, 1 month ago)Clear consciousness Eye: conjunctiva is not pale, anicteric sclera, sunken eyes, no exophthalmos, no eyelid retractionNeck: supple, no JVE, no palpable lymph node, no goiterChest: symmetric and clear breathing soundHeart: regular heart beat, no murmurAbdomen: soft, no abdominal tenderness, normoactive bowel sound, no hepatosplenomegalyBack: no costovetebral angle knocking pain Extremities: free movable, pulses of bilateral dorsalis pedis artery and posterior tibial arteries are normal, no hand tremorSkin: decreased skin turgor*

*

ValuesGlucose AC (mg/dl)308Glucose PC (mg/dl)420HbA1C (%)12.5Total cholesterol (mg/dl)216HDL-C (mg/dl)67LDL-C (mg/dl)132Triglyceride (mg/dl)85Cr (mg/dl)0.73ALT (U/L)17Ca (mg/dl)8.9TSH (U/ml)0.6Free T4 (ng/dl)1.07

*

ValuesUrine albumin/Cr ratio (g/mg)3.7 10g (128 Hz)

*White C. N Engl J Med 2007;356:1241-50.

Values (Ankle Brachial Index)1.02;0.92

*David A. Antonetti et al. N Engl J Med 2012;366:1227-39Arteriolar narrowing (AN)Nerve-fiber hemorrhage (NFH)Hard exudates (HE)Cotton-wool spots (CWS)Venous beading (VB)Preretinal hemorrhage (PRH)

1)2)Genetic defects in -cell functionGenetic defects in insulin actionDiseases of the exocrine pancreas (such as cystic fibrosis)Drug- or chemical induced (such as in the treatment of HIV/AIDS or after organ transplantation)*Modified from Diabetes Care 2012;35:Supplement 1:S11-63Modified from 2012 ,

*Diabetes Care 2004; 27(7): 1798-811Modified from 2012 ,

12 30 40 2Acanthosis NigricansPCOS C- C-ICAAnti-GAD65ICA512ICAAnti-GAD65ICA512

100 mg/dl 140 mg/dl23*DIABETES CARE 2009, 32, 1327-34Pima IndianFPG2hPGHbA1c (1)

(IFG): 100~125 mg/dl(IGT):752 140~199 mg/dl= 5.76.4%*DIABETES CARE 2009, 32, 1327-34FPG2hPGHbA1c(2)

*DIABETES CARE 2009, 32, 1327-34FPG2hPGHbA1c: (A1C) 6.5% * 126 mg/dl *82 200 mg/dl *75() + 200 mg/dl * In the absence of unequivocal hyperglycemia, criteria 13 DM(3)Pima Indian

*Diabetes Care 2012;35:Supplement 1:S11-63

A1C (%) (mg/dl)6126715481839212102401126912298

Gerich JE. Arch Intern Med 163:1306,2003*

Glucose Elevated and Fluctuated in Patients with T2DMAdapted from Monnier et al. Diabetes Care 2007;30:263269*

Modified from Clin. Pharmacol. Ther. 81, 636-649 (2007)*

*Ralph A. DeFronzo. DIABETES 2009, 58, 773-795 -cell-cell

*Adapted from Diabetologia 2003; 46:319http://www.saddoboxing.com/Boxing-Posters/i892498.htmlPima Indians

*Diabetologia 2003;46:3-19

*DeFronzo RA, DIABETES, 2009, 58, 773-795(Islet amyloid polypeptide)

Modified from Stratton IM, et al. BMJ 321;405-412,2000:*

Diabetes 2010, 59:12541260Diabetologia 2010, 53:15411544*

*Modified from 2012 ,

A1C

*2012 ,

15 g/1,000 kcal 7%200mg-3 15-20%0.8 g/kg/day0.81.0g/kg/day0.8g/kg/dayeGFR < 30 ml/min/1.73m20.6g/kg/day0.75g/kg/day1 standard drink1 15 g

*

GI100GIGI (GI)GI (GI)(433)(5311)(5613)(604)(616)(673)(786)(7910)(835)(8710)(919)(941)(1035)(1076)(1329)(32) (36)(47)(523)(5521)(57)(571)(605)(6020)(664)(738)(745)(758)(80) (842)(8411)(103)

*

GI100GIGI (GI)GI (GI)()(54-60)(66)(778)(957)(10810)(2112) (31)(47) (614)(774)(10324)(837) (97)(111)(274)(663)(787)(977)(1414)Adapted from : www.bhp.doh.gov.tw/bhpnet/portal/PressShow.aspx?No=2010051400011.Foster-Powell K, Holt SH, Brand-Miller JC. International table of glycemic index and glycemic load values: 2002.1,2 Am J Clin Nutr 2002; 76(1):556.2.

*2012 ,

22150320 38-12

Diabetes Care 31:111, 2008*

A1C(%)1.02.01Metformin1.02.0Insulin1.53.514Sulfonylurea1.02.0(glibenclamidechlorpropamide)TZDs0.51.4(pioglitazone), (pioglitazone) (rosiglitazone)GLP-1 agonist0.51.0, -Glucosidase inhibitor0.50.8,3,Glinide0.51.53DPP-4 inhibitor0.50.8

*Ralph A. DeFronzo. DIABETES 2009, 58, 773-795

*2012 ,

Metformin1.2.1.5 mg/dl1.4 mg/dl30 ml/minmetformin802metformin3.4.GliclazideGlimepirideGlibenclamideGlipizideNateglinideRepaglinideMitiglinide1.2.3.4.Nateglinide Repaglinide Mitiglinide

*2012 ,

Pioglitazone1.2.5 III IV 2.6-12 3.4.MiglitolAcarbose1.2.3.4.-4 SitagliptinSaxagliptinVildagliptinLinagliptin1.2.

*2012 ,

-1ExenatideLiraglutide1.2.30 ml/min3.1.2.3.4.metformin

*

Adapted from American Journal of Kidney Diseases, Vol 49, No 2, Suppl 2 (February), 2007: pp S13-S154*

CKD Stages 3, 4, or Kidney Transplant sulfonylureas Chlorpropamide 50%GFR

Adapted from American Journal of Kidney Diseases, Vol 49, No 2, Suppl 2 (February), 2007: pp S13-S154*

CKD Stages 3, 4, or Kidney Transplant Meglitinides Repaglinide Nategilnide Initiate at low dose, 60 mg before each meal TZD Pioglitazone Rosigiltazone Incretin mimetic Exenatide Amylin analog Pramlintide No dose adjustment necessary for GFR 20-50 mL/min/1.73 m2 No data available DPP-4 inhibitor Sitagliptin 50% (50mg/day) when GFR < 50 and 30 mL/min/1.73 m275% (25 mg/day) when GFR < 30 mL/min/1.73 m2 75% (25 mg/day)

Endocr Pract. 2009 Sep-Oct;15:540-59.*

MetforminDPP4 inhibitorGLP-1 aginistSulfonylureaGlinideTZD-glucosidase inhibitorInsulin/SevereNeutralNeutralModerateModerateModerateNeutralNeutral/Use with caution in CHFNeutralNeutralNeutralNeutralMild/ModerateNeutralNeutral unless with TZDContraindicted in class 3,4 CHF

*Diabetologia. 2012 Jun;55(6):1577-96.

*Adapted from N Engl J Med 2005;352:174-83.Clinical Diabetes 2009; 27:60-68

Once daily, BID, TID, Basal Bolus regimenEfficacy Side effectsConvenienceCost*

*Diabetologia. 2012 Jun;55(6):1577-96.

Modified from CLINICAL DIABETES 2005, 23; 78-86*

Modified from CLINICAL DIABETES 2005, 23; 78-86*

Modified from CLINICAL DIABETES 2005, 23; 78-86*

*Diabetes Care 2005, 28, 260-265Diabetes Care 2008, 31:852856PREFER Study, Diabetes, Obesity and Metabolism, 2008Exp Clin Endocrinol Diabetes 2006; 114: 511-519

StudyRegimenDM Duration (yrs)A1C Improved (%)Insulin Dose(U/kg/D) HypoglycemiaBW gain INITIATEBasal Glargine vs. BIAsp BID9.20.4 0.28(0.55 vs. 0.83)NS Yang (China)BIAsp bid vs. tid7.90.36 0.04 (0.82 vs. 0.86)NSNS PREFERBIAsp bid vs. Basal-Bolus (Detemir +Asp)9.30.33 0.24(0.63 vs. 0.87)NS LigthelmBIAsp tid vs. Basal-Bolus (NPH +Asp) 13.5-0.05(NS)0.01(1.06 vs. 1.05)NSNS

Increase Insulin Dose, Improve A1C and Gain BWMonnier L, Colette C. Diabetes Metab 2006;32:7-13 Insulin dose < 0.5U/kg/day:0.2 U/kg/day 1% A1C 2kg Insulin dose > 0.5U/kg/day:0.2 U/kg/day 0.5% A1C 2kg

Summary from 6 studies using Glargine, NPH or rapid-acting insulin analogue*

*2012 ,

: ,,3 3//13-6:/eGFR//13-611 10g ,128 Hz,1 1

*45704045213031302150-6921: http://www.bhp.doh.gov.tw/BHPNet/Web/HealthTopic/TopicBulletin.aspx?id=200802190001&parentid=200712250030

*2012 ,Philip E. Cryer. J Clin Invest 2007,117:868870

15-20g50%20-50 ml0.5-1.0 mg152-3

*-470 mg/dl 2012 ,

*2012 ,

(,)140-180 mg/dl < 140 mg/dl < 180 mg/dl

2*

**black figures are shown for addition of insulin glargine; open figures areshown for addition of NPH insulin or rapid-acting insulin analogue).