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Impaired Glucose Tolerance and Risk for Morbidity

Impaired Glucose Tolerance and Risk for Morbidity. Yolanda Y. Clay-Po, M.D. Resident Grand Rounds April 6, 1999. Case Presentation.

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Impaired Glucose Tolerance and Risk for Morbidity

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  1. Impaired Glucose Tolerance and Risk for Morbidity Yolanda Y. Clay-Po, M.D. Resident Grand Rounds April 6, 1999

  2. Case Presentation • H.N. is a 44 year old African-American male who presented to Reynolds Health Center walk-in clinic requesting a 3-hour glucose tolerance test because he wanted to make sure he was not a diabetic. He had been told that he had an elevated blood sugar at an outside hospital one week previously • The patientwas told that glucose tolerance testing was not necessary to diagnose diabetes.

  3. ROS-negative for polyuria,polydipsia,or polyphagia PMH-none PSH-none FH-positive for Diabetes mellitus in mother maternal aunts and uncles SH-no tobacco, no ETOH, no illegal drugs currently Case presentation

  4. Case presentation • Vitals: BP 124/74 weight 240 lb. Afebrile • Physical exam-General: mildly obese male in no distress • HEENT: no scleral icterus,mucosa moist • neck: no JVD, no thyromegaly • chest: clear to auscultation • CVS: regular rhythm,rate normal, no murmurs • Abdomen: obese,bowel sounds present,non-tender no organomegaly appreciated • extremities without edema

  5. Case Presentation • At the patient’s request, a 3-h OGTT was performed

  6. Laboratory Data

  7. Patient questions • Am I a diabetic? • What do you mean I have glucose intolerance? • What can I do to prevent diabetes

  8. Clinical Questions? • What is diabetes mellitus type 2? • How is diabetes diagnosed? • What are the screening criteria?

  9. Diabetes mellitus diagnostic criteria • Diagnostic criteria for Diabetes mellitus type 2 (DM 2) have recently been redefined by the Expert Committee on diagnosis and Classification of Diabetes • there were no changes made in the treatment of diabetes or the treatment goals for diabetes • changes were made in an attempt to diagnose diabetes earlier and to prevent the complications of diabetes from occurring

  10. How to Diagnose Diabetes Mellitus • There are three ways to diagnose diabetes mellitus: • Symptoms + random glucose > 200mg/dl • Fasting Glucose>126mg/dl • Oral glucose tolerance testing with a 2-hour post glucose load of > 200mg/dl

  11. Who should be Screened for Diabetes? • >45 years • <45 with the following risk factors for diabetes: • obesity • first degree relative with DM • member of a high risk population • gestational diabetes or delivery of an infant >9lbs. • History of impaired glucose tolerance or impaired fasting glucose • hypertension or hypertriglyceridemia >250mg/dl

  12. Diagnosis of Diabetes Mellitus • Hemoglobin A1c(Hba1c) has been studied for use in the diagnosis of diabetes but is not recommended as a diagnostic test because of: • wide variability in the methods used in studies • difficulty in assigning cutpoints as with glucose levels • variability of normal ranges

  13. Why were criteria revised? • FPG was found to be identical to 2-hPG in measuring the development of retinopathy in Pima Indians • FPG was an easier test to administer • FPG had easily reproducible results • low cost screening test

  14. Pathophysiology of Insulin Resistance

  15. Progression to Diabetes Mellitus • The mechanism of conversion from IGT to diabetes is not known • It is suspected that it is a two part mechanism • insulin resistance>>inc.glucose concentrations>>increased insulin secretion>> beta cell failure

  16. Diagnosis of Impaired Glucose Tolerance • Impaired glucose tolerance was defined by the Expert Committee as • Fasting Plasma glucose of 110-125mg/dl • 2-hour post glucose load 140-199mg/dl

  17. Clinical questions • Is glucose intolerance a risk factor for other diseases? • How will this evidence help me in advising my patient? • Should glucose intolerance be treated as a true disease state?

  18. Impaired Glucose Tolerance and Coronary Artery Disease

  19. Diabetes Mellitus and CAD risk • Pan et al. Am J Epidem vol 123,vol. 3 504-516 also examined the relationship between hyperglycemia and the risk of CAD • objective: to ascertain if a sex differential existed in the risk of death from CAD • study type: epidemiological • subjects 19,252 Caucasians without previous MI selected from a cohort of theChicago Heart Association Detection Project in Industry

  20. Diabetes Mellitus and CAD risk • Methods: 19,252 persons (11,220 males, 8030 females) were screened with a 50-g glucose load • other CAD risk factors were screened for including cholesterol levels, blood pressure and EKG abnormalities

  21. Diabetes Mellitus and CAD • Relative Risk: • Normal men: normal women 4.87 • DM men: DM women 3.27 • DM men:Normal women 5.91 • DM women/Normal men 1.06

  22. Diabetes Mellitus and CAD risk • Men were more vulnerable than women to heart disease • Men with DM 2 had an increased risk of dying compared to non-diabetic males • age-adjusted risk of a woman with DM 2 was the same as that of a man without DM 2

  23. Diabetes Mellitus and CAD risk • Problems: • Standard dosing of 75-g load was not used • patients divided into groups based on a single value from a test known to have widely variable responses • excluded population of interest

  24. Impaired Glucose Tolerance and Coronary Artery disease Risk • Meigs et al. Ann. Int. Med. 128: 524-533 1998 (Framingham Offpring study) • study type: cross-sectional study • study goal: examine the relationship between metabolic risk factors for CAD and glucose intolerance • participants: 2874 members of the cohort not known to have diabetes

  25. IGT and CAD risk • Method: 75-g glucose tolerance test performed on participants without diabetes • glucose tolerance determined using 1980 WHO criteria • risk factors for CAD were assessed including: • blood pressure • body mass index • HDL cholesterol and triglyceride levels • serum insulin levels • cigarette smoking

  26. IGT and CAD risk • 2.5% of NGT women and 3.8% of NGT men had 4+ risk factors • 17.7% of IGT women and 29.2% of IGT had 4+ risk factors • 38.9% of DM 2 women and 43.7% of DM 2 men had 4+ risk factors • these data imply that persons with IGT are in an intermediate risk category for CAD

  27. IGT and CAD risk • Levels of all Metabolic risk factors increased with each incremental change by quintiles in glucose tolerance • Those found to have previously undiagnosed DM 2 had higher levels of all risk factors • The number of persons with 4+ risk factors increased with increasing glucose tolerance • There was no distinct threshold above which metabolic risk increased

  28. IGT and CAD • Follow-up for this group of patients is very complete • Participants are from a community not a tertiary referral center so referral bias is not likely • unbiased criteria were used to measure outcome (HTN,BMI etc.) • age adjustment was performed for important risk factors

  29. Problems • Average age of patients studied was 54 years • population was predominantly Caucasian • criteria used for diagnosis of DM 2 had lower cutpoints

  30. Progression to Diabetes

  31. Progression to Diabetes • The mechanism of conversion from IGT to diabetes is not known • It is suspected that it is a two part mechanism • insulin resistance >> inc.glucose concentrations >> increased insulin secretion >> beta cell failure

  32. Progression to Diabetes • Viswanathan et al Diabetes Res and Clin Prac 35 (1997) 107-112 • investigated the relationship between weight loss and progression to diabetes • 119 non-diabetic offspring of diabetic parents underwent 2-h GTT with a 75-g glucose load to establish glucose tolerance status • The participants were then given dietary advice based on their body mass index

  33. Dietary advice 60% carbohydrate 20% protein 20% fat avoid sweets,refined sugar Exercise advice walking jogging aerobics Progression to Diabetes

  34. Progression to Diabetes • All participants had individualized physician and registered dietician follow-up to assess compliance for the entire study period

  35. Progression to Diabetes • Results • progression to diabetes occurred in 14.5 % of study participants • In the normal group 6% progressed to diabetes while 19.3 % became IGT • In the EGI group16.1% became diabetics and 26% progressed to IGT • In the IGT group 30.4% became diabetics and 21.4% had normal glucose tolerance

  36. Progression to Diabetes • Rate of development of diabetes was greatest in those who gained weight (p<0.002) • Weight gain most commonly occurred in noncompliant persons • NGT was most common in those who maintained their body weight or lost weight

  37. Progression to Diabetes • Limitations • waist-to-hip ratio was not measured in this study which may underestimate the role of increased abdominal fat in the progression to diabetes • The effect of change in fat distribution could not be evaluated

  38. Progression to Diabetes • Pan et alDiabetes Care vol 20 no. 4,April 1997 • Clinical Question: Do diet and exercise interventions delay the progression of IGT to diabetes? • Methods: 110,660 people screened for IGT and diabetes with a fasting PG and 2h GTT • 577 identified as IGT • 530 subjects (283 male/247 female)were followed for a 6-year period

  39. Progression to Diabetes • Clinics were randomized to interventions • diet only • exercise only • diet and exercise • control group

  40. Exercise advice counselling increase level of exercise type of exercise and rate dependent on age and exercise patterns indoor exercise in winter Diet advice 55-65% carbohydrate 10-15% protein 25-30% fat inc. vegetables moderate ETOH dec. sweets regularly scheduled counseling sessions Progression to Diabetes

  41. Diet + Exercise similar to previous diet and exercise groups Control Group general informations on diabetes given Clinic M.D.’s dispensed brochures on diet and exercise No counseling Progression to Diabetes

  42. Progression to Diabetes • Subjects systematically followed with general medical exam in 2 year intervals with repeat FPG and 2-h GTT • Those with diabetes had reached the endpoint of the study • each group was analyzed separately and compared by several variables

  43. Progression to Diabetes • Results • the incidence of diabetes in the control group was higher than any of the intervention groups at 15.7/100 person years (95% CI, 12.7-18.7%) • NO significant difference was found between the intervention groups: • diet group:10/100 py (95% CI, 7.5-12.5) • exercise group:8.3/100 py (95% CI, 6.4-10.3) • diet + exercise group 9.6/100 py (95% CI,7.2-12.0)

  44. Progression to Diabetes • Baseline physical activity was not predictive in the development of diabetes • The rate of development of diabetes was greater in the obese subjects compared with the lean subjects across all intervention groups

  45. Progression to Diabetes • When compared with the control group there was a: • 33% reduction in the incidence of diabetes in the diet only group (p<0.03) RR=.67 • 47% reduction in the exercise only group(p<.0005) RR=.53 • 38% reduction in the diet+ exercise group RR=.62

  46. Progression to Diabetes • Conclusions: • lifestyle interventions can be effective in reducing the incidence of diabetes mellitus in persons with IGT • There was no significant difference between the effectiveness of the different interventions

  47. Progression to Diabetes • Concerns • Subjects were assigned to clinics who then administered the interventions • can results be generalized to my patient?

  48. Progression to Diabetes • EAT LESS • MOVE MORE

  49. Impaired Glucose Tolerance and Retinopathy

  50. IGT and Retinopathy • Rajala et al. Diabetes Care vol 21,no.10, Oct. 1998 • Study type: cross sectional study • Objective: appraise the ability of the new diabetes criteria to distinguish between those at high risk for retinopathy and those at low risk • subjects: 1,008 persons born in 1935 in Oulu, Finland were screened

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