DM in OPD for Internist. Rungnapa Laortanakul, MD Maharat Nakhon Ratchasima hospital 28 Oct 2013

Transcription

1 DM in OPD for Internist Rungnapa Laortanakul, MD Maharat Nakhon Ratchasima hospital 28 Oct 2013

2 Outlines DM management GDM

3 Case Somjit is a 43-year-old woman Check-up No abnormal symptom Laboratory FBS Cholesterol Triglyceride HDL LDL Creatinine 102 mg/dl 245 mg/dl 230 mg/dl 45 mg/dl 123 mg/dl 1.0 mg/dl

4 Criteria for the diagnosis of diabetes FPG 126 mg/dl Fasting is defined as no caloric intake for at least 8 h 2-h plasma glucose 200mg/dL during an 75g.OGTT Random plasma glucose 200 mg/dl In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis In the absence of unequivocal hyperglycemia Result should be confirmed by repeat testing

5 Prediabetes FPG 100 to 125 mg/dl = IFG 2-h plasma glucose 140 to 199 mg/dl during an 75g.OGTT = IGT A1C % Prediabetes should be tested yearly

6 Case Somjit is a 43-year-old woman Check-up No abnormal symptom 75g.OGTT: BS= 110,220mg/dL HbA1C 7.2 Laboratory Repeat FBS Cholesterol Triglyceride HDL LDL Creatinine 111 mg/dl 245 mg/dl 230 mg/dl 45 mg/dl 123 mg/dl 1.0 mg/dl

7 DM? Glycemic goal? Aim of glycemic control? Diabetic complication? New Diabetic Patient

8 Screening!! Diabetic retinopathy Diabetic nephropathy Diabetic neuropathy PAD

9 Guideline

10 Glycemic Treatment Targets* American Diabetes IDF 2 AACE 3 Association 1 HbA 1c (%) <7.0 < FPG mmol/l (mg/dl) < (70-130) <6.0 (<110) <6.1 (<110) PPG mmol/l (mg/dl) <10 (<180) <8.0 (<145) 7.8 (<140) *Treatment targets for non-pregnant adults. AACE = American Association of Clinical Endocrinologists; FPG = fasting plasma glucose; IDF = International Diabetes Foundation; PPG = postprandial plasma glucose. 1. American Diabetes Association. Diabetes Care. 2012;35(Suppl 1):S11-S International Diabetes Federation (IDF). Available at: Accessed 9 March Handelsman Y, et al. Endocr Pract. 2011;17(Suppl 2):1-53.

11 Thai Guideline การควบค ม เบาหวาน เป าหมาย ควบค มเข มงวดมาก ควบค มเข มงวด ควบค มไม เข มงวด ระด บน าตาลในเล อด ขณะอดอาหาร ระด บน าตาลในเล อดหล ง อาหาร 2 ช วโมง ระด บน าตาลในเล อด ส งส ดหล งอาหาร มก./ดล. 90- <130 มก./ดล. ใกล เค ยง 130 มก./ดล. <140 มก./ดล. - <180 มก./ดล. <180 มก./ดล. HbA1C < 6.5% < 7.0% % แนวทางเวชปฏ บ ต สาหร บโรคเบาหวาน 2554

12 General Therapy Recommendations

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14 Thai guideline 2011 FBS < 180 & HbA1C < 8 Lifestyle modification 3 month FBS mg/dl MF or SU Cut-point BMI 23 FBS or HbA1C >9 2 OHG combination MF, SU, TZD, basal insulin FBS > 300 or HbA1C > 11 3 OHG or add NPH hs OHG = oral hypoglycemic agent

15 Anti-hyperglycemic drugs Thai guideline 2008

16 At the time of type 2 diabetes diagnosis, Initiate metformin therapy along with lifestyle interventions, unless metformin is contraindicated. If noninsulin monotherapy at maximal tolerated dose does not achieve or maintain the A1C target over 3 6 months, add a second oral agent, a GLP-1 receptor agonist, or insulin. ADA 2012

17 First-line type 2 diabetes drug Reducing hepatic glucose production Reduce insulin resistance Weight-neutral with chronic use Does not increase the risk of hypoglycemia Side effects: Initial gastrointestinal side effects Lactic acidosis Caution in advanced renal insufficiency, alcoholism Rare complication Metformin

18 Diabetes Care 32:

19 People with diabetes should be advised Moderate-intensity aerobic physical activity 50 70% of maximum heart rate At least 150 min/week Spread over at least 3 days per week Physical activity

20 Case Somsak is a 64-year-old man was diagnosed with T2DM, HT, and dyslipidemia 9 years ago. No history of hypoglycemia and cardiovascular disease -Glipizide (5) 2 tab bid.ac -Losartan (100) 1 tab OD -Metformin (500) 2 tab bid.pc -Simvastatin (10) 1 tab hs

21 Laboratory Fasting plasma glucose 154 mg/dl HbA1C 8.9 % Cholesterol 145 mg/dl Triglyceride 130 mg/dl HDL 45 mg/dl LDL 88 mg/dl Creatinine 1.0 mg/dl What would you recommend to improve his glycemic control?

22 Medical history Age and characteristics of onset of diabetes Eating patterns, physical activity habits, nutritional status, and weight history Diabetes education history Review of previous treatment regimens and response to therapy (A1C records) DIABETES CARE

23 Medical history Current treatment of diabetes, including Medications and medication adherence Meal plan Physical activity patterns Readiness for behavior change Results of glucose monitoring and patient s use of data DIABETES CARE

24 Medical history DKA frequency, severity, and cause Hypoglycemic episodes Hypoglycemia awareness Any severe hypoglycemia: frequency and cause History of diabetes-related complications Microvascular Macrovascular Other: psychosocial problems, dental disease DIABETES CARE

25 Physical examination Height, weight, BMI Blood pressure : orthostatic measurements Fundoscopic examination Thyroid palpation Skin Acanthosis nigricans Insulin injection sites Comprehensive foot examination DIABETES CARE

26 Laboratory evaluation A1C, every 2 3 months If not performed/available within past year: Fasting lipid profile: total, LDL, and HDL cholesterol and triglycerides Liver function tests Test for UAE with spot urine albumin-to-creatinine ratio Serum creatinine and calculated GFR Thyroid-stimulating hormone in Type 1 diabetes Dyslipidemia Women over age 50 years DIABETES CARE

27 Guideline

28 Glycemic Treatment Targets* American Diabetes IDF 2 AACE 3 Association 1 HbA 1c (%) <7.0 < FPG mmol/l (mg/dl) < (70-130) <6.0 (<110) <6.1 (<110) PPG mmol/l (mg/dl) <10 (<180) <8.0 (<145) 7.8 (<140) *Treatment targets for non-pregnant adults. AACE = American Association of Clinical Endocrinologists; FPG = fasting plasma glucose; IDF = International Diabetes Foundation; PPG = postprandial plasma glucose. 1. American Diabetes Association. Diabetes Care. 2012;35(Suppl 1):S11-S International Diabetes Federation (IDF). Available at: Accessed 9 March Handelsman Y, et al. Endocr Pract. 2011;17(Suppl 2):1-53.

29 Thai Guideline การควบค ม เบาหวาน เป าหมาย ควบค มเข มงวดมาก ควบค มเข มงวด ควบค มไม เข มงวด ระด บน าตาลในเล อด ขณะอดอาหาร ระด บน าตาลในเล อดหล ง อาหาร 2 ช วโมง ระด บน าตาลในเล อด ส งส ดหล งอาหาร มก./ดล. 90- <130 มก./ดล. ใกล เค ยง 130 มก./ดล. <140 มก./ดล. - <180 มก./ดล. <180 มก./ดล. HbA1C < 6.5% < 7.0% % แนวทางเวชปฏ บ ต สาหร บโรคเบาหวาน 2554

30 N Engl J Med 2012;366:

31 Laboratory Fasting plasma glucose 154 mg/dl HbA1C 8.9 % Cholesterol 145 mg/dl Triglyceride 130 mg/dl HDL 45 mg/dl LDL 88 mg/dl Creatinine 1.0 mg/dl What would you recommend to improve his glycemic control?

32 Correlation of A1C with average glucose

33 Contribution (%) HbA 1c Is a Combination of FPG and PPG PPG FPG 0 < >10.2 HbA 1c Range (%) The relative contribution of PPG and FPG varies with HbA 1c The clinical significance of improvement in postprandial hyperglycemia has not been established As patients HbA 1c level approaches the healthy range, PPG takes on greater importance in determining HbA 1c. FPG = fasting plasma glucose. Monnier L, et al. Diabetes Care. 2003;26(3):

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35 Glinides Short duration Three times/day dosing, expensive Diabetologia (2006) 49: Diabetes Care 2012;35: Antidiabetic interventions as monotherapy Interventions Expected decrease in HbA1c (%) Advantages Disadvantages Lifestyle interventions 1-2 Low cost, many benefits Fails for most in first year Metformin 1.5 Weight neutral, inexpensive GI side effects, rare lactic acidosis Insulin No dose limit, inexpensive, improved lipid profile Injections, monitoring, hypoglycaemia, weight gain Sulfonylureas 1.5 Inexpensive Weight gain, hypoglycaemia TZDs Improved lipid profile Fluid retention, weight gain, expensive DPP IV inhibitor No hypoglycemia, Well tolerated α-glucosidase inhibitors Urticaria/angioedema? Pancreatitis Weight neutral Frequent GI side effects, three times/day dosing, expensive Exenatide Weight loss Injections, frequent GI side effects, expensive, little experience

36 Insulin secretagogues Stimulate insulin release Through the closure of ATP-sensitive potassium channels on β-cells Associated with modest weight gain and risk of hypoglycemia Glibenclamide, Glipizide, Gliclazide, Glimepiride Sulfonylurea

37 Peroxisome proliferator activated receptor γ activators Improve insulin sensitivity in skeletal muscle and reduce hepatic glucose production Not increase the risk of hypoglycemia May be more durable in their effectiveness than sulfonylureas and metformin Thiazolidinediones (TZDs)

38 Pioglitazone Modest benefit on CV events as a 2 outcome in one large trial involving patients with overt macrovascular disease Possible increased risk of bladder cancer Side effects Weight gain Fluid retention leading to edema ± Heart failure in predisposed individuals Increased risk of bone fractures Rosiglitazone No longer widely available >> Increased myocardial infarction risk Thiazolidinediones (TZDs)

39 Oral drug Regulation of insulin and glucagon secretion Weight neutral Not increase the risk of hypoglycemia Sitagliptin (Januvia), Vidagliptin (Galvus) Dipeptidyl peptidase 4 (DPP-4) inhibitors

40 Decrease gut carbohydrate absorption But have gastrointestinal effects, mainly flatulence and constipation Acarbose (Glucobay), Vogibose (Basen) α-glucosidase inhibitors (AGIs)

41 Incretin system Injectable GLP-1 receptor agonists Stimulating pancreatic insulin secretion in a glucose-dependent Suppressing pancreatic glucagon output Slowing gastric emptying Decreasing appetite Weight loss in most patients GLP-1 receptor agonists

42 Side effect : Nausea and vomiting, particularly early in the course of treatment Increased risk of pancreatitis GLP-1 receptor agonists

43 Anti-hyperglycemic drugs Thai guideline 2008

44 Case Somsak is a 64-year-old man was diagnosed with T2DM, HT, and dyslipidemia 9 years ago. No history of hypoglycemia and cardiovascular disease -Glipizide (5) 2 tab bid.ac -Losartan (100) 1 tab OD -Metformin (500) 2 tab bid.pc -Simvastatin (10) 1 tab hs Add Pioglitazone (30) 1x1 oral OD

45 SMBG Self-monitor blood glucose

46 Case 3 month later Somsak is a 64-year-old man was diagnosed with T2DM, HT, and dyslipidemia 9 years ago. No history of hypoglycemia and cardiovascular disease -Glipizide (5) 2 tab bid.ac -Metformin (500) 2 tab bid.pc -Losartan (100) 1 tab OD -Simvastatin (10) 1 tab hs -Pioglitazone (30) 1x1 oral OD FBS 155 mg/dl, HbA1C 8.2

47 Day ac pc ac pc ac pc hs Pre/post-prandial hyperglycemia

48 Anti-hyperglycemic drugs Thai guideline 2008

49 The steps of insulin treatment Setting glucose control goal Initiating insulin therapy Titration of insulin dose Intensification of treatment regimen DIABETES CARE, VOLUME 36, SUPPLEMENT 2, AUGUST 2013

50 Postprandial glucose measure 1 2 h after meal A1C <,7.0% Preprandial capillary plasma glucose mg/dl Peak postprandial capillary plasma glucose <180 mg/dl Goals should be individualized based on* Duration of diabetes Age/life expectancy Comorbid conditions Known CVD or advanced microvascular complications Hypoglycemia unawareness Individual patient considerations More- or less-stringent glycemic goals may be appropriate for individual patients Summary of glycemic recommendations

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52 ADA 2009 Start : NPH 10 unit SC hs Typically by 2 unit every 3 days If hypoglycemia, reduce 4 unit or 10%

53 Basal insulin is preferable when adding insulin therapy to antidiabetes drugs. 3 exceptions... Patients with relatively low fasting or preprandial glucose (<150 mg/dl) despite high HbA1C Patients with difficulty in compliance with the high demands of basal-bolus treatment Patients in whom self-titration might not be feasible Initiating insulin therapy DIABETES CARE, VOLUME 36, SUPPLEMENT 2, AUGUST 2013

54 Case Somsak is a 64-year-old man was diagnosed with T2DM, HT, and dyslipidemia 9 years ago. No history of hypoglycemia and cardiovascular disease -Glipizide (5) 2 tab bid.ac -Metformin (500) 2 tab bid.pc -Losartan (100) 1 tab OD -Simvastatin (10) 1 tab hs -Pioglitazone (30) 1x1 oral OD Add NPH 10 unit sc hs

55 NPH 10 unit sc hs Day ac pc ac pc ac pc hs month later

56 The steps of insulin treatment Setting glucose control goal Initiating insulin therapy Titration of insulin dose Intensification of treatment regimen DIABETES CARE, VOLUME 36, SUPPLEMENT 2, AUGUST 2013

57 Pharmacokinetic Profiles of Insulin Insulin type Onset Peak Duration Long-acting Detemir Glargine 2 hr 2 4 hr No peak No peak Intermediate-acting NPH 1-3 hr Short-acting Aspart/Glulisine/Lispro Regular 15 to 30 min. 30 to 60 min. 30 to 90 min. 2 to 4 hr 3 to 5 hr 5 to 8 hr Mixed NPH/lispro or aspart NPH/regular 15 to 30 min. 30 to 60 min. Dual Dual 14 to 24 hr 14 to 24 hr J Clin Endocrinol Metab, May 2012, 97(5): Am Fam Physician. 2011;84(2):

58 When basal insulin fails to achieve the target in spite of titration, the physician should proceed to insulin intensification. 3 common regimens... Premix Basal plus Addition of rapid-acting insulin with one of the daily meals Basal bolus Addition of rapid insulin with 2-3 daily meals Insulin intensification DIABETES CARE, VOLUME 36, SUPPLEMENT 2, AUGUST 2013

59 Once-daily glargine, detemir, or NPH therapy Am Fam Physician. 2011;84(2):

60 Basal-bolus insulin Am Fam Physician. 2011;84(2):

61 Premix insulin Am Fam Physician. 2011;84(2):

62 Most patients who begin a basal plus regimen will eventually need a basal-bolus regimen; therefore, basal plus regimen should be initiated if the treating physician decides that the patient will be able to adhere to a basal-bolus regimen. Basal bolus most closely resembles physiological insulin secretion Premix insulin analogs can be a good option with less complicated and demanding glucose monitoring and injection schedule Insulin Regimens DIABETES CARE, VOLUME 36, SUPPLEMENT 2, AUGUST 2013

63 Diabetes Care 2012;35:

64 Which patient should be offered a premix vs basal-bolus/basal plus regimen? Premix insulin analogs Patient preference Older age Need assistance with injections Organaized lifestyle Two meals a day or evening main meal Basal plus/basal bolus Type 1 DM Younger age Highly motivated and compliance Active lifestyle High variability in eating habits DIABETES CARE, VOLUME 36, SUPPLEMENT 2, AUGUST 2013

65 Rationale for initiating basal versus premix insulin analogs DIABETES CARE, VOLUME 36, SUPPLEMENT 2, AUGUST 2013

66 Initiation and intensification of premix insulin analogs DIABETES CARE, VOLUME 36, SUPPLEMENT 2, AUGUST 2013

67 NPH 10 unit sc hs Day ac pc ac pc ac pc hs Divide basal insulin to 2/3 dose in morning and 1/3 evening NPH 10 unit sc hs -Switch 4 to Mixtard (70/30) 12 unit sc ac with breakfast and 6 unit sc with dinner

68 Using Insulin with Oral Medications Insulin secretagogues (sulfonylureas and glitinides) can be combined with insulin, especially when only basal augmentation is being used. However, there is a possible increased risk of hypoglycemia that needs to be monitored closely. Usually by the time insulin is required for meals, insulin secretagogues are not effective or necessary. However, it is recommended to continue oral medications while starting insulin to prevent rebound hyperglycemia. After the diabetes is controlled, the patient may be weaned off of oral medications Am Fam Physician. 2011;84(2):

69 Using Insulin with Oral Medications Insulin sensitizers have been proven safe and effective when combined with insulin therapy Metformin,Thiazolidinediones, Alphaglucosidase inhibitors, DPP-IV inhibitor (Sitagliptin), etc. Am Fam Physician. 2011;84(2):

70 Case Somsak is a 64-year-old man was diagnosed with T2DM, HT, and dyslipidemia 9 years ago. No history of hypoglycemia and cardiovascular disease -Glipizide (5) 1 tab bid.ac -Metformin (500) 2 tab bid.pc -Losartan (100) 1 tab OD -Simvastatin (10) 1 tab hs -Pioglitazone (30) 1x1 oral OD -Mixtard (70/30) 12 unit sc ac with breakfast and 6 unit sc with dinner

71 Severely uncontrolled diabetes with catabolism : Fasting plasma glucose > 250 mg/dl Random glucose levels > 300 mg/dl HbA1C > 10% Presence of ketonuria Symptomatic diabetes with polyuria, polydipsia and weight loss Insulin therapy in combination with life-style intervention is the treatment of choice. Special considerations/patients

72 In newly type2 DM with markedly symptomatic ± elevated blood glucose levels or A1C, consider insulin, with or with additional agents High baseline HbA1c (e.g. 9.0%) Low probability of achieving a near-normal target with monotherapy. May combination of 2 noninsulin agents or with insulin itself in this circumstance

73 Summary of recommendations Glycemic, BP, and lipid control for diabetes A1C < 7.0% Blood pressure <130/80 mmhg LDL cholesterol <100 mg/dl

74 Screening for and diagnosis of GDM Perform a 75-g OGTT Fasting plasma glucose and at 1 and 2 h at weeks gestation in women not previously diagnosed with overt diabetes The OGTT should be performed in the morning after an overnight fast of at least 8 h. The diagnosis of GDM is made when any of the following : Fasting 92 mg/dl 1 h 180 mg/dl 2 h 153 mg/dl GDM

75 Target maternal capillary glucose Preprandial 95mg/dL and 1-h postmeal 140mg/dL or 2-h postmeal 120mg/dL

76 Pre-existing diabetes who are planning pregnancy or who have become pregnant should have a comprehensive eye examination and be counseled on the risk of development and/or progression of DR. Eye examination should occur in the first trimester with close follow-up throughout pregnancy and for 1 year postpartum. Pregnancy

77 During pregnancy with chronic hypertension Target blood pressure goals SBP mmhg DBP mmhg Antihypertensive drugs known to be effective and safe in pregnancy Methyldopa Labetalol Diltiazem Clonidine Prazosin HT and Pregnancy