Faculty Bibliography

A 71 year old woman with Type 2 diabetes mellitus (Type 2DM), chronic kidney disease stage IV (CKD stage IV), primary hypothyroidism, and osteoarthritis whose prescribed treatment included miglitol 50 mg thrice daily with the first bite of meals reported that she suffered visual hallucinations while taking miglitol, which resolved within a few days of stopping the drug. When she resumed miglitol hallucinations recurred within a few days and again resolved within a few days of stopping the drug. At no point were hallucinations associated with any symptom of hypoglycemia or a low finger stick glucose reading. Glycemic control was suboptimal with HbA1c by HPLC = 11.2%. She was still hypothyroid on thyroxine replacement with TSH by chemiluminescence = 39.7 mIU/ml.Although, in general, miglitol is minimally absorbed following oral administration (2-3%) it is mostly eliminated unchanged via the renal route and thus, may accumulate, in the setting of renal failure. Likewise, incompletely compensated hypothyroidism may result in drug accumulation. Once absorbed, miglitol is able to cross the blood/brain barrier and potentially inhibit the alpha-glucosidase enzymes of the the central nervous system (CNS), eg isomaltase, resulting in CNS glycogen accumulation mimicking genetic glycogen storage diseases, eg Pompe disease, which may also present with hallucinations. Inhibition of CNS alpha-glucosidases may also result in formation of aneurysms. Although one series has reported a 2% incidence of hallucinations in patients taking the related drug, acarbose, the risk is not widely appreciated and it is not a reported adverse effect in the package insert for either medication.We conclude that alpha-glucosidase inhibitors should be used with caution in patients with coexisting renal insufficiency and incompletely treated hypothyroidism. CNS changes, in the absence of hypoglycemia should dictate drug discontinuation

AIM: To provide evidence based recommendations for optimal care diabetes care in the elderly. BACKGROUND: Diabetes affects approximately 25% of the population >/=65 years, and that percentage is increasing rapidly, particularly in minorities who represent an important fraction of the uninsured/underinsured. Diabetes is an important cause of hospital admissions and a co-morbidity in as high as 50% of hospital inpatients. It impacts mortality and quality of life. While tools have become available to improve glycemic control, enthusiasm for their application must be tempered with the sober realization of the risks involved in intensification of glycemic control, chiefly hypoglycemia. RESULTS/CONCLUSIONS: Weighted review from PubMed and other literature search tools in descending order of randomized control trials, observational studies, pilot studies, published guidelines, the authors' clinical experience, and expert opinion

OBJECTIVE: To study the effect of adding metformin to standard steroid replacement therapy in a patient with classic salt-losing congenital adrenal hyperplasia due to 21-hydroxylase deficiency with suboptimal biochemical and clinical control. METHODS: We present the clinical and laboratory findings before and after the addition of metformin to the therapeutic regimen of the study patient. RESULTS: A 17-year-old girl had been diagnosed as a neonate with classic salt-losing congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CYP21A2 deficiency). She was treated with hydrocortisone, 20 mg in the morning and 10 mg at bedtime, and fludrocortisone, 50 mcg daily. While on steroid replacement, she maintained normal serum electrolytes, glucose, blood pressure, and external genitalia, but she continued to express clinical features of obesity, hirsutism, amenorrhea, and acanthosis nigricans. Elevated laboratory measurements included the following: fasting 17-hydroxyprogesterone, 3410 ng/dL; total testosterone, 326 ng/dL; and androstenedione, 390 ng/dL. She was initiated on metformin, 500 mg twice daily after meals. After 3 months, the patient lost 2 kg, amenorrhea resolved, 17-hydroxyprogesterone decreased to 1539 ng/dL, total testosterone decreased to 163 ng/dL, and androstenedione levels remained unchanged. CONCLUSIONS: Metformin, an agent known to reduce insulin resistance, further suppressed the 17-hydroxyprogesterone concentration in a patient with classic congenital adrenal hyperplasia on steroid replacement therapy. Metformin may improve clinical and biochemical outcomes in classic congenital adrenal hyperplasia without the risk of iatrogenic Cushing syndrome

OBJECTIVE: To ascertain an association between the a priori known insulin resistance caused by antipsychotic agents and divalproex and adrenal hyperandrogenism and to determine whether the associated hyperandrogenism is reversible with insulin sensitizers. METHODS: We studied 26 consecutive psychiatric inpatients (22 women and 4 men) receiving the aforementioned medications, who were referred to us for a consultation. They ranged in age from 19 to 79 years and had a mean body mass index (SEM) of 32.35 +/- 1.26 kg/m2. Between 8 AM and 9 AM, blood samples were collected for 17-hydroxyprogesterone, 17-hydroxypregnenolone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate, 11-deoxycortisol, luteinizing hormone and follicle-stimulating hormone (in reproductive age women), estrone, estradiol (in reproductive age women), free testosterone (in women), deoxycorticosterone, and sex hormone-binding globulin (SHBG), which were measured by radioimmunoassay, after chromatography if necessary. For intact, premenopausal women, measurement of the abnormal steroid metabolite or SHBG level was repeated during prednisone therapy (5 mg at bedtime) to document the likely adrenal origin of the abnormality. Men, women who had undergone bilateral oophorectomy, and postmenopausal women had hyperandrogenism of adrenal origin by default. Clinical features included central obesity, acanthosis, hirsutism, alopecia, type 2 diabetes mellitus, and oligomenorrhea. RESULTS: We found reversed estrone/estradiol ratios in 4 patients, decreased SHBG in 4, increased 17-hydroxy-pregnenolone in 8, increased 17-hydroxyprogesterone in 2, increased deoxycorticosterone in 2, increased DHEA sulfate in 1, increased 11-deoxycortisol in 4, increased androstenedione in 1, and reversed ratios of luteinizin hormone to follicle-stimulating hormone in 2. The bio-chemical abnormalities were corrected in 8 of 8 patients receiving metformin and in 2 of 2 patients receiving rosiglitazone. CONCLUSION: Insulin resistance caused by antipsychotic agents and divalproex is associated with adrenal hyperandrogenism. Metformin and rosiglitazone correct the biochemical abnormalities detected without compromising their psychotropic effect. Adrenal androgen synthesis may be increased by hyperinsulinemia-induced hyperphosphorylation of P450c17 alpha, resulting in an increase in its 17,20-lyase activity, which magnifies the effects of any distal steroidogenic enzyme defects. Treatment with metformin or rosiglitazone prevents excess adrenal androgen synthesis

Osteoporosis is a major public health problem with low bone mass affecting nearly half the women aged 50 years or older. Evidence from various studies has shown that higher body mass index (BMI) is a protective factor for bone mineral density (BMD). Most of the evidence, however, is from studies with Caucasian women and it is unclear to what extent ethnicity plays a role in modifying the effect of BMI on BMD.A cross sectional study was performed in which records of postmenopausal women who presented for screening for osteoporosis at 2 urban medical centres were reviewed. Using logistic regression, we examined the interaction of race and BMI after adjusting for age, family history of osteoporosis, maternal fracture, smoking, and sedentary lifestyle on BMD. Low BMD was defined as T-score at the lumbar spine < -1.Among 3,206 patients identified, the mean age of the study population was 58.3 +/- 0.24 (Years +/- SEM) and the BMI was 30.6 kg/m2. 2,417 (75.4%) were African Americans (AA), 441(13.6%) were Whites and 348 (10.9%) were Hispanics. The AA women had lower odds of having low BMD compared to Whites [Odds ratio (OR) = 0.079 (0.03-0.24) (95% CI), p < 0.01]. The odds ratio of low BMD was not statistically significant between White and Hispanic women. We examined the interaction between race and BMD. For White women; as the BMI increases by unity, the odds of low BMD decreases [OR = 0.9 (0.87-0.94), p < 0.01; for every unit increase in BMI]. AA women had slightly but significantly higher odds of low BMD compared to Whites [OR 1.015 (1.007-1.14), p <0.01 for every unit increase in BMI]. This effect was not observed when Hispanic women were compared to Whites.There is thus a race-dependent effect of BMI on BMD. With each unit increase in BMI, BMD increases for White women, while a slight but significant decrease in BMD occurs in African American women