Rational Therapeutics in Diabetes Mellitus

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Selected Endocrine Problems in HIV Sugar, Bones,
and Sex Hormones
Todd T. Brown, MDAssistant Professor of
MedicineThe Johns Hopkins University
From TT Brown, MD, at 12th Annual Ryan White
HIV/AIDS Program Clinical Conference, IASUSA.
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DIAGNOSIS OF DIABETES 2009

• HgbA1c ? 6.5
• Confirm elevated value with repeat measurement,
  unless symptoms of diabetes plus casual plasma
  glucose ?200 mg/dL
• If A1c not valid (hemoglobinopathy, increased red
  cell turnover), FPG and 2-hour post-load glucose
  

Diabetes Care, July , 2009
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Definition of Pre-Diabetes American Diabetes
Association
To be replaced by A1c 6.0-6.5
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Glucose Higher in HIV vs. Control for a given
HbA1c
? ? HIV (n100) - - - ? Control (n200)
Glucose (mg/dL)
A1c Discordance 29 mg/dL
Kim, Diabetes Care, 2009
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Message to Patients You need both to have
diabetes, but only one you have control
over. Diabetes is not necessarily a one way
street. Weight loss is key. Metabolically
relevant weight loss is about 10 body weight
(i.e. different from cosmetically relevant
weight loss)
Insulin Resistance Environmental
ß-cell Dysfunction Genetic
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Evaluation of Glucose Disorders in HIV-infected
Patients
Fasting glucose (at HIV diagnosis, antiretroviral
therapy initiation, and annually thereafter)
lt 100 mg/dL
100-125 mg/dL
126 mg/dL
Repeat FG 126 mg/dL?
Yes
No
2-hr OGTT
140-199 mg/dL
200 mg/dL
lt 140 mg/dL
Repeat fasting glucose in 1 year
IFG/IGT
DM
IFG alone
DM
Lifestyle modifications, metformin or
pioglitazone
Lifestyle modifications
Lifestyle modifications, consider metformin with
other RFs, consider pioglitazone with lipoatrophy
Brown, CCO, 2008
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2008 US National Osteoporosis Foundation (NOF)
Guidelines for DXA Screening

• Those with a history of fragility fracture
• Women 65 yrs, Men 70
• Postmenopausal women and men 50-70 years, if
  there is concern based on risk factor profile

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Definitions

• Functional Definition (DXA)- WHO Definition
• Osteoporosis T-score ? -2.5
• Osteopenia T-score between -1.0 and -2.5
• Normal T-score ? -1.0
• ? Risk of fracture by 1.5-3.0 x for each SD
  decrease
• Caveats
• Z-score (?-2.0) used in men lt 50 years and
  premenopausal women
• BMD explains only about 50 of fracture risk

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Secondary Causes of Low BMD

• Vitamin D deficiency? 25 OH Vit D
• Hyperparathyroidism? PTH, Ca
• Subclinical Hyperthyroidism? TSH
• Hypogonadism? Males Testosterone Females
  Menstrual History
• Phosphate wasting? Serum Phosphate
• Idiopathic Hypercalciuria? 24 hr Urinary Calcium
• Celiac Sprue? Tissue Transglutaminase
• Multiple Myeloma? Serum Protein Electrophoresis
• Mastocytosis ? Serum Tryptase
• Cushings Syndrome ? 24 hr Urinary Free Cortisol

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Osteomalacia

• Impaired bone mineralization
• Accompanied by weakness, fracture, pain,
  anorexia, and weight loss
• Severe vitamin D deficiency and phosphate wasting
  most common causes
• Treated with Vitamin D, Ca, /- phosphate, not
  bisphosphonates
• Most important differential diagnosis for low BMD

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Treatment of Vitamin D Deficiency

• Definitions
• Deficiency 25 OH Vitamin D lt 20 ng/mL
• Insufficiency 25 OH Vitamin D between 20-30
  ng/mL
• Vitamin D Replacement- Filling Up the Tank
• Ergocalciferol 50,000 units twice a week for 8-12
  weeks
• Vitamin D Maintenance
• Cholecalciferol 800-1200 IU each day (over the
  counter)
• Ergocalciferol 50,000 units every 2-4 weeks

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Considerations When Choosing Between
Bisphosphonates
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Diagnosis of Androgen Deficiency in HIV-infected
Men
Symptoms consistent with androgen deficiency with
no other obvious explanation.
Obtain free testosterone levels.
Case 2 Total T 232 ng/dL Free T 32 ng/dL (nl
46-224) Bioavailable T 63 ng/dL (nl 110-575)
Start with morning free testosterone given
possible SHBG abnormalities
Mylonakis E, et al. Clin Infect Dis.
200133857-864.
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Suggested Monitoring During Testosterone Treatment
Months