Dr. Ron’s Research Review – June 17, 2010

Dr. Wright,

This week's research review continues last week’s topic of insulin resistance with some information on lab tests that use fasting insulin and glucose – the HOMA and QUICKI indexes.

Both Dr. Wright and I agree that the 4-hour Glucose-Insulin Tolerance Test (GITT) with the Kraft Criteria provides the most detailed information and is the preferred test for insulin resistance. Fasting tests only provide a brief snapshot.

We also have an article relating hormones (testosterone) with insulin resistance: Erectile Dysfunction, Obesity, Insulin Resistance, and Their Relationship with Testosterone Levels in Eugonadal Patients in an Andrology Clinic Setting

Copper Deficiency

Acquired copper deficiency is a potentially serious and preventable complication following gastric bypass surgery. (Griffith, Liff et al. 2009)

Celiac disease can cause copper deficiency. (Halfdanarson, Kumar et al. 2009)

Copper deficiency may cause of reversible anemia and neutropenia. (Jabbour, DiGiuseppe et al. 2010) (Harless, Crowell et al. 2006)

In the News:

Bioidentical hormones for menopausal symptoms By Chris Woolston, LA Times, Link

Bad medical writing hurts public health By Otis Brawley, CNN Link

Dr. Ron

Homeostasis Model Assessment

The Homeostasis Model Assessment (HOMA) index is calculated according to the formula:

serum glucose (mg/dL) x insulin (uU/mL) ÷ 405.

Insulin resistance is defined as a HOMA ≥ 3. (Matthews, Hosker et al. 1985) (Yokoyama, Emoto et al. 2004)

Quantitative Insulin Sensitivity Check Index

The quantitative insulin sensitivity check index (QUICKI) is calculated as: (Katz, Nambi et al. 2000)

1 ÷  ( log (fasting plasma insulin in U/ml) + log (fasting plasma glucose in mg/dl) )

By my calculations, HOMA = 3 is equivalent to QUICKI = 0.324


Erectile Dysfunction, Obesity, Insulin Resistance, and Their Relationship with Testosterone Levels in Eugonadal Patients in an Andrology Clinic Setting

(Knoblovits, Costanzo et al. 2009) Download

Erectile dysfunction (ED) is associated with metabolic and endocrine diseases including obesity, metabolic syndrome (MS) and Type 2 Diabetes Mellitus (DM2). Insulin-resistance (IR), present in patients with obesity, MS and DM2, causes disturbances in the signaling pathways required for nitric oxide production with subsequent endothelial dysfunction. In addition, IR also appears to alter testosterone production. We evaluated in eugonadal ED patients: 1) the presence of obesity and IR; 2) testosterone levels and their association with obesity and IR and 3) the degree of ED according to the presence of IR. In a prospective study 78 eugonadal patients with ED (group P) where recruited and compared with 17 men without ED as a control group (group C). The erectile function was evaluated according the International Index of Erectile Function 5 (IIEF-5). IR was measured by HOMA. IR was defined as a HOMA >/= 3. Results: patients with ED had a significant higher BMI, waist circumference (WC), HOMA values an prevalence of IR when compared to group C. Total (TT) and bioavailable testosterone (BT) levels were lower in group P compared to group C. There was a significantly negative correlation between HOMA and IIEF-5, HOMA and TT, WC and IIEF-5, WC and TT and between WC and BT. Group P patients with IR had a higher WC and lower IIEF-5 score when compared with patients in group P without IR. In conclusion: Patients with ED show a higher BMI, WC, and HOMA and lower levels of TT and BT. There is a negative correlation between erectile function and IR and abdominal obesity. The TT levels are lower in patients with increased BMI, WC and IR. However, a negative correlation was shown only between BT (biologically active fraction) and abdominal obesity.

Acquired copper deficiency: a potentially serious and preventable complication following gastric bypass surgery

            (Griffith, Liff et al. 2009)

Copper is an essential cofactor in many enzymatic reactions vital to the normal function of the hematologic, vascular, skeletal, antioxidant, and neurologic systems. Copper deficiency in the United States is believed to be relatively rare but has been described in the setting of zinc supplementation, myelodysplastic syndrome, use of parenteral nutrition and chronic tube feeding, and in various malabsorptive syndromes, including following gastrectomy and gastric bypass surgery. Features of copper deficiency include hematologic abnormalities (anemia, neutropenia, and leukopenia) and myeloneuropathy; the latter is a rarer and often unrecognized complication of copper deficiency. We here describe two patients who presented with severe gait abnormalities and anemia combined with neutropenia several years after roux-en-Y gastric bypass (RYGB) surgery for obesity who were found to be severely copper deficient. Intravenous copper repletion resulted in the rapid correction of hematologic indices; combined intravenous and oral copper supplementation and eventual oral copper supplements alone normalized serum copper levels in each patient, but resulted in only partial resolution of the neurologic deficits. This report serves to alert physicians of the association between RYGB procedures and subsequent copper deficiency in order to avoid diagnostic delays and to improve treatment outcomes.

Copper deficiency in celiac disease

            (Halfdanarson, Kumar et al. 2009)

Copper deficiency is an uncommonly reported complication of celiac disease that has not received much attention in recent years. Copper deficiency may result in anemia and thrombocytopenia and also irreversible myeloneuropathy if it is not detected and treated appropriately. The prevalence of copper deficiency in patients with celiac disease is unknown. We describe 5 patients with celiac disease and associated copper deficiency diagnosed at our institution in recent years. All 5 patients had neurologic complications of copper deficiency and 3 patients also presented with hematologic abnormalities. We also review the literature regarding copper deficiency in celiac disease.

Anemia and neutropenia associated with copper deficiency of unclear etiology

(Harless, Crowell et al. 2006)

Copper deficiency is rarely reported as a cause of neutropenia and anemia through mechanisms not clearly understood. Most cases have been found in malnourished infants or persons receiving total parenteral nutrition without adequate copper. We report on two otherwise healthy young adults with severe neutropenia and anemia secondary to copper deficiency of unclear etiology, which quickly resolved after supplementation with copper gluconate. Both women consumed excessive quantities of soft drinks, which may have contributed to the development of their copper deficiency. Two cases of an unexplained copper deficiency anemia and neutropenia in otherwise healthy young adults found at a single institution over a short period of time suggests that this problem may be more widespread than is currently realized.


Griffith, D. P., D. A. Liff, et al. (2009). "Acquired copper deficiency: a potentially serious and preventable complication following gastric bypass surgery." Obesity (Silver Spring) 17(4): 827-31.

Halfdanarson, T. R., N. Kumar, et al. (2009). "Copper deficiency in celiac disease." J Clin Gastroenterol 43(2): 162-4.

Harless, W., E. Crowell, et al. (2006). "Anemia and neutropenia associated with copper deficiency of unclear etiology." Am J Hematol 81(7): 546-9.

Jabbour, N., J. A. DiGiuseppe, et al. (2010). "Copper deficiency as a cause of reversible anemia and neutropenia." Conn Med 74(5): 261-3.

Knoblovits, P., P. R. Costanzo, et al. (2009). "Erectile Dysfunction, Obesity, Insulin Resistance, and Their Relationship with Testosterone Levels in Eugonadal Patients in an Andrology Clinic Setting." J Androl.