Diabetes Update Timothy C. Evans, MD PhD FACP Department of Medicine and MEDEX Northwest University of Washington

Transcription

1 Diabetes Update 2017 Timothy C. Evans, MD PhD FACP Department of Medicine and MEDEX Northwest University of Washington

2 NCCPA Disclaimer I am on the Board of Directors (BOD) of NCCPA. The BOD is involved with strategic direction and policy. The BOD does not develop or review the exams. I have never taken nor seen the PANCE, PANRE, or individual test items. In this lecture I am not speaking on behalf of the NCCPA, nor with any knowledge of specific exam test items.

3 Topics Diagnosis/Standards of Care Diabetic Foot Evaluation Rx including New Drugs A Word About Thiazolidinediones What Should the Glucose Goal Be? Metabolic Syndrome and DM prevention What s Next?

4 Types of Diabetes Type 1 Autoimmune, insulin deficient, DKA prone Type 2 Familial, insulin resistance and abnormal insulin secretion Gestational Other Drug induced, endocrinopathies, genetic

5 Diagnostic Criteria FPG 126 mg/dl Random PG 200 mg/dl in a patient with Sx of hyperglycemia 2-hr PPG 200 mg/dl during OGTT ADA Rec: Screen high risk pts q 3 yrs HbA 1c (2010, became an official diagnostic criterion) Prediabetes, % Diabetes, 6.5% or greater

6 Who to Screen BMI > 25 kg/m 2 (> 23 kg/m 2 Asian Amer) and: Phys inact; +1 st deg rel with DM; Hx GDM; HBP; HDL < 35 mg/dl and/or TG > 250 mg/dl; women with PCOS; HbA 1c > 5.7%, IGT, IFG; cond assoc with ins resist (severe obesity, acanthosis nigricans); Hx CVD. Start at age 45 yrs Repeat q3yrs, more freq for pre-dm or other risks

7 Standards of Care Diabetes Care (journal) Supplement, each January Accessible at SoC 2016, Abridged for Primary Care Providers at: Abridged-SOC.pdf

8 Standards of Care Glycemic Control Whole blood values Normal Goal Additional Action Suggested Average preprandial glucose (mg/dl) < <80 or >140 Average bedtime glucose (mg/dl) < <100 or >160 Plasma values Average preprandial glucose (mg/dl) < <90 or >150 Average bedtime glucose (mg/dl) < <110 or >180 HbA 1c (%) <6 <7 >8

9 Standards of Care Weight and Diet Diet: 50+% calories from carbohydrate, < 30% calories from fat (mostly monounsaturated, < 7% sat, < 200 mg chol, min trans FA), 15-20% from protein (0.8 g/kg) Weight control for overwt or obese: kcal/d deficit. Inc insulin sensitivity in type 2. Bariatric surgery consider in BMI > 35kg/m 2

10 Standards of Care Exercise Attention to micro and macrovascular dis Gradual increase ETT if 10% 10-yr cardiac event risk 150+ min/wk mod ex (50 70 % max ht rt) Or 90+ min/wk vigorous aerobic ex (> 70% max ht rt) Spread over at least 3 d/wk, no more than 2 consecutive days of inactivity

11 Prevention of Complications Hypertension Goal < 140/90 (lower?, JNC 8) Regimen should include ACEI or ARB, esp if also nephropathy Add CCB, thiazide, others Lifestyle smoking cessation, diet (DASH, mod EtOH, sodium < 2.4 g/d), physical activity (mod-vig 3-4 days/wk, 40 min/session)

12 Prevention of Complications Dyslipidemia ATP 4 Four statin benefit groups Clinical ASCVD LDL > 190 mg/dl DM, yrs, LDL mg/dl yrs, LDL mg/dl, 10-yr risk 7.5% or higher, no DM or ASCVD

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14 New Risk Calculator 10-yr risk for ages years Similar risk factors to Framingham Sex, age, race, total cholesterol, HDLcholesterol, systolic BP, Rx for HBP, diabetes, smoking Diabetes not an automatic ASCVD risk equivalent ledcohort.aspx

15 Statin Intensity High lowers LDL by > 50% atorv mg, rosuv mg Moderate lowers LDL by 30 to < 50% atorv 10-20, rosuv 5-10, simva 20-40, similar moderate doses for the other statins Low lowers LDL by < 30% simva 10 mg, similar low doses other statins, no atorv or rosuv

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17 ASCVD Risk 50 y/o, Tchol 250 mg/dl, HDL 38 mg/dl, SysBP 145 mmhg, HTN Rx yes, smoker no DM no, 10-yr ASCVD risk 9.1% DM yes, 10-yr ASCVD risk 16.8%

18 ASCVD Risk 50 y/o, Tchol 200 mg/dl, HDL 38 mg/dl, SysBP 145 mmhg, HTN Rx yes, smoker no DM no, 10-yr ASCVD risk 6.7% DM yes, 10-yr ASCVD risk 12.5%

19 ASCVD Risk 50 y/o, Tchol 200 mg/dl, HDL 40 mg/dl, SysBP 125 mmhg, HTN Rx no, smoker no DM no, 10-yr ASCVD risk 4.2% DM yes, 10-yr ASCVD risk 7.9%

20 Prevention of Complications Smoking Cessation & ASA Use Smoking quit all tobacco products 1/4 1/2 ASA for 2º CVD prevention Use for 1º prevention in: > 50 y/o with other RF (+ FH, HBP, smoking, dyslipidemia, albuminuria), or Pts with 10-yr CHD risk 10%

21 Prevention of Complications Retinopathy Dilated exam by specialist Type 1 within 3-5 yrs of Dx Type 2 at Dx Before, during, and after pregnancy for preexisting DM

22 Mohamed, Q. et al. JAMA 2007;298: Nonproliferative and Proliferative Diabetic Retinopathy A: Moderate nonproliferative diabetic retinopathy with microaneurysms, retinal hemorrhages, and macular edema characterized by increased vascular permeability and deposition of hard exudates at the central retina. B: Proliferative diabetic retinopathy with new vessels and fibrous tractional bands arising from the optic disc.

23 Prevention of Complications Nephropathy Annual microalbuminuria and egfr Type 1 after 5 years Type 2 at Dx Rx micro or macroalbuminuria ACEI or ARB Dietary protein, 0.8 mg/kg (~ 10% daily cal) Control BP also with ACEI, ARB, diuretics, CCB

24 Prevention of Complications Neuropathy At Dx in type 2, after 5 yrs in type 1 Foot exam Autonomic screening hypoglycemic unawareness, resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunct Pain can be treated with pregabalin, duloxetine, and tapentadol. For more severe: amitriptyline, venlafaxine, gabapentin, opioids.

25 Prevention of Complications Foot Care Exam 10-gram monofilament; vascularization; vibration; proprioception; palpation; visual exam for callus, skin atrophy or ulceration, infection, nail care, hair distribution, deformity Pt education, glycemic control, D/C smoking, orthotics

26 Likelihood of Osteomyelitis Visible bone or ability to probe to bone Ulcer > 2 x 2 cm Ulcer duration > 1 2 wks ESR > 70 mm/hr

27 The Primary Cause of Amputations Shoes and socks at clinic visits The time to take them off You can save limbs if you look at feet. Efficiency Get the shoes and socks off before you come into the room Train your patients Instruct the office staff

28 Treatment Insulin Type 1 DM Multiple daily injections of insulin, basal and prandial, with individualization, multiple SMBG Type 2 DM for very high blood sugars, as augmentation for oral agents, basal or multiple duration insulin. Individualize. Insulin should be used more often than it is.

29 Insulin preparations Insulin Preparations Onset of Action Peak Action Duration of Action Lispro/Aspart 5 15 minutes 1 2 hours 4 6 hours Human Regular minutes 2 4 hours 6 10 hours Human NPH 1 2 hours 4 8 hours hours Glargine/Detemir 1 2 hours Flat ~24 hours

30 Treatment Drugs Oral Agents (type 2 DM): Insulin secretagogues Sulfonylureas Meglitinides Insulin sensitizers Metformin Thiazolidinediones Polysaccharide digestion inhibitors alphaglucosidase inhibitors Dipeptidyl peptidase IV (DPP-IV) inhibitors Sodium-glucose transporter 2 (SGLT 2) inhib

31 Expected HbA 1c Decrease TLC 1-2% Metformin 1-2% (slow) Sulfonylureas 1-2% (fast) Insulins % (fastest) TZDs % (slowest) GLP-1 agonists % α-glucosidase inhibs % DPP-IV inhibs % SLGT-2 inhibs 1%

32 The Incretin Effect More rapid disposal of glucose load when given by mouth than IV Greater insulin effect Glucagon inhibition Delayed gastric emptying Due to GI signaling and release of GI hormones

33 GI Hormones and an Enzyme Inhibitor Glucagon-like peptide 1 (GLP-1), injectable, nausea exenatide, ER-exenatide, liraglutide Amylin ( gastric emptying, satiety), injectable, nausea pramlintide Dipeptidyl peptidase IV (DPP-IV, rapidly degrades GLP-1 and GIP) inhibitors, oral sitagliptin, saxagliptin, linagliptin, alogliptin

34 Na-Glucose Transporter Inhibitors SGLT-2 in proximal renal tubule Canagliflozin Accounts for 90% glucose reabsorption Decrease HbA 1c by ~1%, BW and SBP Yeast vaginitis, UTI, polyuria, occas hypoglycemia Contraindications type 1 DM, severe renal insufficiency

35 Thiazolidinediones Cardiac Effects Bones

36 Pioglitazone Pioglitazone meta-analysis 19 trials; 16,390 patients Decreased death, MI, CVA; HR 0.82 ( ) Increased CHF; HR 1.41 ( ) No change CHF mortality Prescribing information includes black box warning about CHF JAMA. 2007;298:

37 Rosiglitazone Rosiglitazone meta-analysis 4 RCTs; 14,391 patients Increased MI; HR 1.42 ( ) CHF; HR 2.09 ( ) No change cardiac mortality; HR 0.90 ( ) Prescribing information includes black box warning about CHF and myocardial ischemia JAMA. 2007;298:

38 More Rosiglitazone Meta-analysis 42 trials Mean age 56 years Baseline HbA 1c 8.2% MI odds ratio 1.43 (95% CI, , P=0.03) CV death odds ratio 1.64 (95% CI, , P=0.06) NEJM. 2007;356:

39 Rosiglitazone vs Pioglitazone 227,571 Medicare patients, mean age 74.4 yrs Rosiglitazone or Pioglitazone for 3 years Acute MI, CVA, CHF, all-cause mortality, composite of all 8667 endpoints, Rosi > Pio for CVA, CHF, death Composite risk 1.68 (95% CI, ) NNH 60 Rx d for 1 year JAMA. 2010;304: JAMA. 2010;304:

40 Thiazolidinediones and Bones Risk of peripheral fractures Both pioglitazone and rosiglitazone FDA warnings in prescribing information JAMA. 2007;297:1645. Drug Saf. 2009;32:

41 Thiazolidinediones For Now Avoid in NYHA Class III and IV CHF Use with caution in Class I and II Prudent to avoid rosiglitazone in patients at significant risk of ischemic ht disease and instead consider metformin, SUs, or insulin Consider fracture risk

42 How Low Should the Glucose Be? DCCT, UKPDS, and long-term benefits Steno-2 and long-term followup ACCORD NEJM. 2008;358: ADVANCE NEJM. 2008;358: VADT NEJM. 2009;360:

43 DCCT Type 1 DM NEJM. 1993;329:

44 Epidemiology of Diabetes Interventions and Complications (EDIC) NEJM. 2005;353:

45 UKPDS Type 2 DM

46 UKPDS 10 Years Later HbA 1c differences gone after 1 year RR decrease in SU/insulin aggressive Rx 9% any DM endpoint 24% microvascular disease 15% MI 13% any cause death RR decrease in metformin aggressive Rx 21% any DM endpoint 33% MI 27% any cause death NEJM. 2008;359:

47 Steno-2 Study and Follow-Up

48 ACCORD

49 ADVANCE 11,140 pts, RCT, HbA 1c goal < 6.5% At 5 years intensive 6.5%, std 7.3% Results Micro/macrovasc; HR 0.90 ( ), 1º renal Major microvasc; HR 0.86 ( ) 1º renal (HR 0.79; ), no effect retinopathy No effect on major macrovasc, CV death, or any cause death Gliclazide 90.5% vs 1.6%, TZD 16.8% vs 10.9% Insulin 40.5% vs 24.1%

50 Veterans Affairs Diabetes Trial

51 Glucose Control in the ICU Early studies showed benefit of tight control. More recent multicenter studies, in both medical and surgical ICUs, show risk. Ideal is probably a compromise between risk of out-of-control DM and hypoglycemia SoC: mg/dl in most critically ill patients. Insulin is preferred treatment.

52 Recommendations for Now HbA 1c 7% remains standard of care Probably more to be gained from getting uncontrolled pts down to 7% than from lowering tightly controlled pts further Attention to healthy lifestyle Diet, exercise, weight control Aggressive BP control Aggressive dyslipidemia control Discontinue tobacco

53 Metabolic Syndrome NCEP (revised 2005, Circulation. 2005;112: ) Any three of five of the following Glucose intolerance/insulin resistance: FBS 110 mg/dl ( 100 mg/dl, or on drug Rx) Hypertension: BP 130/85 (or on drug Rx) Dyslipidemia TG 150 mg/dl (or on drug Rx) HDL < 40 mg/dl in men, < 50 mg/dl in women (or on drug Rx) Central adiposity: waist circ > 40 men, > 35 in women

54 Metabolic Syndrome Prevalence Third NHANES, Arch Int Med. 2003:

55 Metabolic Syndrome and Cardiovascular Mortality JAMA. 2002;288:

56 Cumulative Hazard, % Metabolic Syndrome and Cardiovascular Mortality JAMA. 2002;288:

57 Cumulative Hazard, % Metabolic Syndrome and Cardiovascular Mortality JAMA. 2002;288:

58 Finnish Diabetes Prevention Study Design 522 middle-aged overweight (BMI 31) 172 men and 350 women Mean duration 3.2 years Intervention Group: Individualized counseling Reducing weight, total intake of fat and saturated fat Increasing intake of fiber, physical activity Tuomilehto J et al. N Engl J Med 2001;344:

59 Treating the Metabolic Syndrome Goals Intervention Controls % of subjects P value Wt reduction >5% Fat intake < 30% energy Sat fat <10% energy Fiber >15 g/1000 kcal Exercise > 4 hr/wk Tuomilehto J et al. N Engl J Med 2001;344:

60 Incidence of Diabetes (%) Incidence of Diabetes during Follow-up Control Intervention No. with Diabetes/Total no. Success Score Intervention 5/13 10/66 9/69 2/38 0/25 0/24 Control 15/48 25/107 14/48 2/15 0/11 0/4

61 Diabetes Prevention Program NEJM. 2002;346:

62 ADA Recommendations For patients with IGT or IFG Lifestyle intervention is primary Modest wt loss 5 10% Moderate exercise, 30 min daily Smoking cessation For patients with both IGT and IFG consider adding metformin Consider OGTT in pts with IFG less than 60 y/o and with BMI > 35

63 Metabolic Syndrome Summary

64 What s Next? Non-invasive glucose monitoring Type 1 Islet and stem cell transplantation Type 2 Rx the epidemic of obesity Increased understanding of weight homeostasis Mechanism of insulin resistance and the connection with visceral adiposity Genetics of diabetes

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