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Diabetes Mellitus What's new and what hasn't changed Martin C. Young MD Pediatric Endocrinologist Pediatric Specialized Care Rapides Medical Center,

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Presentation on theme: "Diabetes Mellitus What's new and what hasn't changed Martin C. Young MD Pediatric Endocrinologist Pediatric Specialized Care Rapides Medical Center,"— Presentation transcript:

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3 Diabetes Mellitus What's new and what hasn't changed Martin C. Young MD Pediatric Endocrinologist Pediatric Specialized Care Rapides Medical Center, Alexandria LA

4 Defining Diabetes Mellitus (DM)  Chronic hyperglycemia  Acute complications  Chronic complications –macrovascular –microvascular –other

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6 Types of DM  Type 1  Type 2  Other

7 Type 1 & Type 2 DM  Type 1 (IDDM) –childhood infection of pancreas resulting in autoimmune destruction and loss of insulin –insulin dependent  Type 2 (NIDDM) –insulin resistance leading to pancreatic exhaustion –insulin requiring (often)

8 DM is Common 1  Prevalence –world: 150 million –USA: 20 million (6% population)  1/3 all cases undiagnosed  High risk groups –AfroAmerican x2 –Hispanic x2 –American Native x5

9 DM is Common 2  10% of people aged >20 yrs  20% of people aged >60 yrs  USA increase across ages approx 40%

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11 DM is Expensive  US costs per annum >$ 100 billion

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13 Diagnosing DM  Your patient has DM until otherwise proven!

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16 OGTT 1

17 Prediabetes  Impaired fasting glucose (IFG) –FBG mg/dl  Impaired glucose tolerance (IGT) –BG mg/dl at 2 hours on OGTT IFG & IGT are not benign

18 OGTT 2

19 Risk for Death by Fasting and 2-hour Blood Glucose Level <6.16.1–6.9  7.0  –11.0 <7.8 Fasting plasma glucose (mmol/l) 2-hour plasma glucose (mmol/l) Hazard ratio Adjusted for age, center, sex DECODE Study Group. Lancet 1999;354:617–621

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21 Values to Remember  Fasting blood glucose >100 mg/dl –think "pre-diabetes" (IFG)  Random blood glucose > 140 mg/dl –think "prediabetes" (IGT)  Blood glucose > 200 mg/dl at any time –think "diabetes"

22 How DM Presents 1  Classic symptoms –polydipsia & polyuria –weight loss  Accidentally –urinalysis –random blood glucose  Suspiciously –recurrent candidiasis

23 How DM Presents 2  Screening –asymptomatic –high risk groups

24 Screening for DM 1  Aged >45 yrs  Aged <45 yrs, fat plus other risk factor –1 st degree relative with diabetes –physically inactive –high risk ethnic group –hypertension –dyslipidemia

25 Screening for DM 2 –PCOS –IFG or IGT on OGTT previously –Acanthosis nigricans –Vascular disease

26 Screening for DM 3  Fasting blood glucose  OGTT (2 hr)

27 Suspicious of DM?  Random blood glucose  Fasting blood glucose  OGTT  HbA1c (glycated hemoglobin)  Fructosamine (glycated albumin)  GlycoMark (1,5-Anhydroglucitol)

28 Histogram of Serum 1,5AG Concentrations Healthy (n=539) 24.6±7.2 µg/mL Diabetes (n=808) 7.3±7.1 µg/mL Serum 1,5AG (µg/mL)

29 Diabetes & Friends  Associated syndromes  Comorbidities "You're never alone with diabetes"

30 Syndromes Associated with Type 2 DM  Metabolic syndrome (MS)  Polycystic ovarian syndrome (PCOS)  Obstructive sleep apnea syndrome (OSAS)

31 Metabolic Syndrome (MS)  Obesity  Hypertension  Dyslipidemia  Acanthosis nigricans  Abnormal glucose homeostasis A prothrombotic, proinflammatory, atherogenic, endothelial dysfunctional condition.

32 Acanthosis Nigricans 1

33 Acanthosis Nigricans 2

34 Overlap of Type 2 DM and MS

35 Polycystic Ovarian Syndrome  (Polycystic ovaries)  Hyperandrogenemia or hirsuitism  Menstrual disturbance

36 MS, DM, PCOS Overlap The "full catastrophe"

37 OSAS  Obstructive apnea during sleep due to airway occlusion from obesity  Recurrent hypoxemia –pulmonary hypertension –RV strain failure  Recurrent arousal from sleep –daytime fatigue, etc  Hypertension  Atrial fibrillation

38 Why PCOS, MS & OSAS are Related to Type 2 DM  Insulin resistance –causes PCOS and Type 2 DM –can result from OSAS  Hyperinsulinism –hypertension –dyslipidemia –acanthosis nigricans –ovarian production of androgens

39 Non-alcoholic Fatty Liver Disease 1  NAFLD (non-alcoholic steatohepatitis, NASH)  Fatty infiltration of liver assocaited with obesity, MS and Type 2 DM  May progress to cirrhosis

40 Non-alcoholic Fatty Liver Disease 2

41 Type 2 DM 90 % of all diabetes mellitus90 % of all diabetes mellitus 99% all adult diabetes99% all adult diabetes Approaching 30-50% of all childhood diabetesApproaching 30-50% of all childhood diabetes Formally very rare in childrenFormally very rare in children Profoundly underdiagnosed – "silent"Profoundly underdiagnosed – "silent" A disease of genes interacting with the "Western Way" of overeating and underexercisingA disease of genes interacting with the "Western Way" of overeating and underexercising

42 Type 2 DM Pathophysiology Key concept I: insulin resistanceKey concept I: insulin resistance –genetic –obesity –inactivity –OSAS Key concept II: glycemic loadKey concept II: glycemic load –high glycemic index (GI) foods

43 Insulin Resistance

44 Bad Genes & Bad Choices

45 Progression of Type 2 DM PhaseInsulinGlucose 1N 2IGT 3IFG 4N DM -oral meds DM -oral meds 5 DM -insulin

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47 Pancreatic Failure Insufficient insulin to prevent chronic hyperglycemiaInsufficient insulin to prevent chronic hyperglycemia Usually sufficient insulin to prevent ketoacidosisUsually sufficient insulin to prevent ketoacidosis

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49 Look for Comorbidities! Complications of DM Complications of DM –eye disease –vascular disease –neuropathy –nephropathy –dermatopathy Associated syndromes Associated syndromes –MS –PCOS –OSAS –NAFLD/NASH

50 Eye Disease Retinopathy Retinopathy Cataracts Cataracts

51 Vascular Disease Peripheral arterial disease Peripheral arterial disease Ischemic heart disease Ischemic heart disease Cerebral vascular disease Cerebral vascular disease

52 Neuropathy Peripheral sensory neuropathy Peripheral sensory neuropathy

53 Nephropathy Urine microalbumin Urine microalbumin

54 Dermatopathy Diabetic ulceration & ischemia Diabetic ulceration & ischemia Necrobiosis Necrobiosis Granuloma annulare Granuloma annulare

55 Associated Syndromes 1 MS MS –acanthosis nigricans –obesity –hypertension PCOS PCOS –hirsuitism –menstrual irregularity –acne

56 Associated Syndromes 2 OSAS OSAS –snoring –restless sleep –night sweats –daytime fatigue/headache NAFLD/NASH NAFLD/NASH –hepatomegaly

57 Tests for the Newly Diagnosed DM patient 1 Eye exam Eye exam ABI (doppler) ABI (doppler) Filament test (nerve conduction) Filament test (nerve conduction) Urine Urine –glucose –ketones –microalbumin

58 Tests for the Newly Diagnosed DM patient 2 Blood Blood –lipid panel –LFTs –TSH –HbA1c, fructosamine, GlycoMark Uncertain Type 2 vs. Type 1 DM? Uncertain Type 2 vs. Type 1 DM? –fasting insulin –diabetes autoimmune screening panel.

59 Treatment of Type 2 DM  Treatment of complications and comorbidities  Medical nutrition therapy (MNT)  Therapeutic exercise (TE)  Oral hypoglycemics  Injectibles –insulin –other

60 Treatment - Obesity  Appetite suppressants  Orlistat (Xenical)  MNT to produce loss of fat  Bariatric sugery

61 Treatment - Hypertension  Antihypertensives –ACE inhibitors –others

62 Treatment - dyslipidemia  Antihyperlipidemic drugs –statins –other

63 Treatment – MS  Aspirin  Statins  MNT

64 Treatment - PCOS  OCP  Spironolactone  MNT  Other

65 OSAS  Tonsillectomy & adenoidectomy  Nasal CPAP  MNT for fat loss.

66 Treatment - Nephropathy  ACE inhibitors  MNT – protein restriction

67 Treatment – Eye Disease  Cataract removal  Laser surgery for retinopathy

68 Treatment - NASH  Alchohol restriction  Antihyperlipidemics  Vitamin E  MNT

69 Medical Nutrition Therapy TraditionalTraditional Non-traditionalNon-traditional

70 MNT – Traditional 1 "Low fat/ high carb diet""Low fat/ high carb diet" –CHO 45-65% of calories –PROT 10-35% –FAT 20-35% –high fiber –low sodium –low cholesterol (<200 mg/d) –low saturated fat (<7% calories)

71 MNT – Traditional 2 For obese patientsFor obese patients –calorie restriction women kcal/dwomen kcal/d men kcal/dmen kcal/d –aim for lb weight loss 1-2 lbs/week EffectivenessEffectiveness –improves glycemic control –reduces BP –improves dyslipidemia –little weight loss – typically 4 lbs after 1 year

72 MNT – Nontraditional 1 Low CHO <130g/d (often <80g/d)Low CHO <130g/d (often <80g/d) Low glycemic index (LGI)Low glycemic index (LGI) VegetarianVegetarian Stone ageStone age

73 Therapeutic Exercise Aerobic exerciseAerobic exercise –at least 30 mins x3/week

74 Drug Therapy Oral Hypoglycemics Oral Hypoglycemics Parenteral medications Parenteral medications Inhaled insulin Inhaled insulin

75 Oral Hypoglycemics 1

76 Oral Hypoglycemics 2 Secretagogues Secretagogues most useful early on Sulfonylureas Sulfonylureas –glyburide (Diabeta) –glipizide (Glucotrol) –glimepiride (Amaryl) Meglitanides Meglitanides –repaglinide

77 Oral Hypoglycemics 3 Insulin sensitizers Insulin sensitizers Biguanides Biguanides –metformin Thiazolidinediones Thiazolidinediones –pioglitazone (Actos) –rosiglitazone (Avandia) –troglitazone (Rezulin)

78 Oral Hypoglycemics 4 Absorbtion blockers Absorbtion blockers glucosidase inhibitors glucosidase inhibitors –miglitol (Glyset) –acarbose (Precose)

79 Oral Hypoglycemics 5 Combination drugs Combination drugs Glucovance Glucovance –metfromin –glyburide Metaglip Metaglip –metformin –glipizide

80 Oral Hypoglycemics 6 Each drug lowers HbA1c by approximately 1-2%

81 Oral Hypoglycemics 7 Polypharmacy is the rule Polypharmacy is the rule Most patients are going to be on at least two drugs Most patients are going to be on at least two drugs Use drugs from different groups Use drugs from different groups

82 Insulins nametrade nametype regular Humulin, Novolin R short NPH Humulin, Novolin N intermediate lisproHumalograpid glulisine Apidra rapid aspartNovolograpid glargineLantuslong detemirLevemirlong

83 Insulin Profiles

84 Regular & NPH Insulins peak actions: R ~ 3 hrs, N ~ 6 hrs

85 Rapid Acting Insulins peak action: ~ 1 hr

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87 Lantus

88 Levemir

89 Mixed Insulins Humulin Humulin Humalog Humalog Novolog Novolog 70/30 70/30 50/50 50/50 75/25 75/25 50/50 50/50 70/30 70/30

90 Insulin Delivery Devices 1 Pens Pens –disposable –rechargable

91 Insulin Delivery Devices 2

92 Insulin Delivery Devices 3

93 Inhaled Insulin Exubera Exubera

94 Other Injectable Drugs 1 Exenatide (Byetta) Exenatide (Byetta) –insulin secretagogue –peptide –gila monster saliva –use with other drugs –no hypoglycemia –bid

95 Other Injectable Drugs 1 Pramlintide (Symlin) Pramlintide (Symlin) –analogue of hormone amylin –polypetide –slows gastric emptying –induces satiety –opposes glucagon reduces posprandial BG –give with meals used with insulin

96 Traditional Rx of Type 2 DM Step 1: MNT &TE Step 1: MNT &TE Step 2: 1 st drug Step 2: 1 st drug Step 3: 2 nd drug Step 3: 2 nd drug Step 4: 3 rd drug Step 4: 3 rd drug Step 5: insulin Step 5: insulin Each step added as satisfactory HbA1c is not achieved by the preceding Each step added as satisfactory HbA1c is not achieved by the preceding Very slow process over months to years Very slow process over months to years

97 Modern "Aggressive" Rx of Type 2 DM from Time of Diagnosis HbA1c > 10 % HbA1c > 10 % –or FPG >260 mg/dl FPG >260 mg/dl –or Symptomatic Symptomatic –or Ketotic Ketotic IMMEDIATE INSULIN

98 Modern "Aggressive" Rx 2 HbA1c 8-10 % HbA1c 8-10 % –e.g Glucovance  2.5/500 bid  max 20/2000 per day Immediate combination oral hypoglycemic drug Immediate combination oral hypoglycemic drug Titrate dose up rapidly every month using short term markers of control Titrate dose up rapidly every month using short term markers of control

99 Modern "Aggressive" Rx 3 HbA1c < 8% HbA1c < 8% Monotherapy with drug of choice Monotherapy with drug of choice Titrate dose up rapidly every month using short term markers of control Titrate dose up rapidly every month using short term markers of control Add further drugs (different actions) if necessary Add further drugs (different actions) if necessary

100 Modern "Aggressive" Rx 4 HbA1c not < 7% by 6 months HbA1c not < 7% by 6 months Start Insulin

101 Insulin Regimens for Type 2 DM Step one: once daily long acting Step one: once daily long acting –Levemir –Lantus Step two: mixed insulin at breakfast Step two: mixed insulin at breakfast Step three: mixed insulin at supper Step three: mixed insulin at supper etc. etc. Titrate to fasting blood glucose Titrate to fasting blood glucose

102 Assessing Rx Success  Measures of glycemic control –HbA1c –fructosamine –GlycoMark –self monitoring of blood glucose (SMBG)

103 Measures of Glycemic Control 1,5A G Fructosamine HbA 1C Blood glucose Weeks before measurement

104 Glycated Hemoglobin (HbA1c) 1

105 Glycated Hemoglobin (HbA1c) 2

106 Glycated Hemoglobin (HbA1c) 3

107 Fructosamine

108 GlycoMark Oral Supply 1,5AG (5-10mg/day) Blood stream Tissues Internal Organs ( mg) Kidne y Urinary excretion (5-10mg/day) Oral Supply 1,5AG (5-10mg/day) Blood Stream (1,5-AG Level Lower) Tissues Internal Organs ( mg) Kidney Urinary excretion (INCREASED) NormoglycemiaHyperglycemia Glucose Blocks Reabsorption

109 SMBG  Value in Type 2 DM not established  Useful for titrating insulin

110 Summary  Increasing prevalence of Type 2 DM  Diagnostic criteria for DM, IGT, IFG  Screening for DM  Comorbidities & associated syndromes  Aggressive Rx of Type 2 DM  New insulins  New measures of glycemic control


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