Levothyroxine dose following thyroidectomy is affected by more than just body weight.

OBJECTIVES/HYPOTHESIS: To determine the factors that affect levothyroxine (LT4) requirements following thyroidectomy. STUDY DESIGN: Retrospective study. METHODS: This study evaluated 246 participants who had undergone total thyroidectomy and were on a stable dose of LT4. Actual weight-based (AWB) and ideal body weight-based (IBWB) LT4 dose requirements were analyzed, and other confounders including adherence, concurrent medications, comorbidities, female menopausal status, and hormone replacement therapy were examined. RESULTS: A total of 205 women and 41 men were evaluated, with 48 (20%) benign and 198 (80%) malignant pathology findings. The mean AWB LT4 doses for men and premenopausal women were similar among members of the benign groups and similar among members of the malignant groups. There was a trend for lower dose LT4 in postmenopausal women off hormonal therapy (PM/NH) and on hormonal therapy (PM/H) in the benign group (1.4 and 1.6 µg/kg vs. 1.8 µg/kg in the men and premenopausal women) and a trend for lower dose LT4 in the PM/H women in the malignant group (1.9 µg/kg vs. 2.1 and 2.2 µg/kg in the men and premenopausal women), but they were not significant. However, PM/NH women required significantly less LT4 (1.7 µg/kg) than both the men (2.2 µg/kg) and premenopausal women (2.1 µg/kg) in the malignant group (P=.0006). The IBWB LT4 dosage was not statistically different between groups. CONCLUSIONS: LT4 dosage following thyroidectomy, calculated using actual body weight, can range from 1.4 to 2.2 µg/kg and is dependent on diagnosis (benign vs. malignant), goal TSH, sex, and menopausal status.

Vitamin D insufficiency is associated with diabetes risk in Native American children.

AIMS/HYPOTHESIS: Vitamin D insufficiency has not been well studied in Native American (NA) children, who are at risk for obesity and diabetes. The authors examined vitamin D insufficiency and its association with body mass index (BMI) and insulin resistance. METHODS: In a cross-section of NA children 5 to 18 years old (N = 198), anthropometrics, biomarkers of insulin resistance, and 25-hydroxy-vitamin D concentration [25(OH) vitamin D] were measured. BMI% and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. RESULTS: Mean age was 10.8 ± 0.3 years (mean ± SEM). Mean serum 25(OH) vitamin D was 17.8 ± 0.4 ng/mL and 97% had vitamin D insufficiency [25(OH) vitamin D <30 ng/mL]. After adjusting for BMI, 25(OH) vitamin D was inversely associated with HOMA-IR (P < .0001) and several other markers of insulin resistance. CONCLUSIONS/INTERPRETATION: Vitamin D insufficiency was nearly universal in this cohort of NA children and was associated with diabetes and vascular risk markers. Whether vitamin D supplementation can improve insulin resistance must be studied further.

Body mass index percentile more sensitive than acanthosis nigricans for screening Native American children for diabetes risk.

BACKGROUND: Many Native American tribes use acanthosis nigricans to screen for type 2 diabetes risk. We hypothesized that acanthosis nigricans misses many children at risk for type 2 diabetes. METHODS: We evaluated 5- to 18-year-old Native American children and youth to assess the sensitivity and specificity of acanthosis nigricans as a marker for insulin resistance. RESULTS: In a cohort of 161 youth (72 males/89 females), mean age was 10.7 years + 3.9. Mean body mass index (BMI) percentile was 76.8 +/- 23.3, and 54% had a BMI at or above the 85th percentile. Acanthosis nigricans was present in 21.7% of the participants and was more common in 12-to 18-year-olds than in 5 to 11-year-olds (p = .02). Of those with acanthosis nigricans, 82.4% had insulin resistance (homeostatic model assessment of insulin resistance >4), but only 48.3% of those with insulin resistance had acanthosis nigricans. In contrast, BMI at or above the 85th percentile had a high sensitivity (74%) for insulin resistance, even though its specificity was lower (58%). CONCLUSIONS: The presence of acanthosis nigricans alone was a specific, but not a sensitive, screening tool for identifying youth with insulin resistance. BMI at or above the 85th percentile was a more sensitive screening tool than acanthosis nigricans alone, or acanthosis nigricans and BMI together for identifying children and youth with IR who are at increased risk for type 2 diabetes.

Hyperglycemia induced by tacrolimus and sirolimus is reversible in normal sprague-dawley rats.

Post-transplant diabetes mellitus (PTDM) worsens outcomes after kidney transplantation, and immunosuppression agents contribute to PTDM. We have previously shown that tacrolimus (TAC) and sirolimus (SIR) cause hyperglycemia in normal rats. While there is little data on the mechanism for immunosuppressant-induced hyperglycemia, we hypothesized that the TAC and SIR-induced changes are reversible. To study this possibility, we compared normal rats treated for 2 weeks with either TAC, SIR, or a combination of TAC and SIR prior to evaluating their response to glucose challenge, with parallel groups also treated for 2 weeks after which treatment was stopped for 4 weeks, prior to studying their response to glucose challenge. Mean daily glucose and growth velocity was decreased in SIR, and TAC+SIR-treated animals compared to controls (P < 0.05). TAC, SIR, and TAC+SIR treatment also resulted in increased glucose response to glucose challenge, compared to controls (P < 0.05). SIR-treated animals also had elevated insulin concentrations in response to glucose challenge, compared to controls (P < 0.05). Insulin content was decreased in TAC and TAC+SIR, and islet apoptosis was also increased after TAC+SIR treatment (P < 0.05). Four weeks after treatments were stopped, all differences resolved between groups. In conclusion, TAC, SIR, and the combination of TAC+SIR-induced changes in glucose and insulin responses to glucose challenge that were accompanied by changes in islet apoptosis and insulin content. These changes were no longer present 4 weeks after cessation of therapy suggesting immunosuppressant-induced changes in glucose metabolism are likely reversible.

The Prevalence of Vitamin D Deficiency Is Similar between Thyroid Nodule and Thyroid Cancer Patients.

Introduction. There are reported associations between vitamin D deficiency and breast, prostate, and colon cancer, but the relationship in thyroid cancer has not been evaluated. Methods. We evaluated serum calcium, creatinine, albumin, and 25-hydroxy vitamin D (25-OH-D) in 42 thyroid nodule, 45 thyroid cancer in remission, and 24 active thyroid cancer patients. Results. 25-OH-D was not different between groups. The percent with 25-OH-D levels <75 nmol/L was not significantly different between groups and was not affected by season of measurement, age, or cancer stage. Multivariate regression showed a BMI of >/=30 kg/m(2) to be the only significant predictor of vitamin D deficiency. Conclusions. Rates of vitamin D deficiency are similar in thyroid nodules and thyroid cancer, although higher than the general population. This is different than previous studies for other cancers, which show higher rates of vitamin D deficiency. BMI was the only predictor of vitamin D deficiency.

Finding the optimal dose of vitamin D following Roux-en-Y gastric bypass: a prospective, randomized pilot clinical trial.

BACKGROUND: Vitamin D deficiency is common following bariatric surgery and is due to a combination of baseline deficiency and postoperative malabsorption. There are few prospective studies evaluating the appropriate dose of vitamin D to prevent and treat vitamin D deficiency following bariatric surgery. METHODS: We evaluated three doses of vitamin D3 (800, 2,000, and 5,000 IU/day) in a prospective, randomized pilot trial of 45 patients undergoing Roux-en-Y gastric bypass. Serum 25 hydroxy Vitamin D (25OHD), intact PTH (iPTH), calcium, and urine calcium/creatinine ratios were measured at 6, 12, and 24 months postoperatively. Due to a high dropout rate at 24 months, we focus on the 12-month data. RESULTS: At 12 months, the 800-, 2,000-, and 5,000-IU groups had a mean +/- SD increase in 25OHD of 27.5 +/- 40.0, 60.2 +/- 37.4, and 66.1 +/- 42.2 nmol/L, respectively (p = 0.09) with a maximum increase in each group of 87.4, 114.8, and 129.8 nmol/L. Forty-four percent, 78%, and 70% achieved 25OHD levels >or=75 nmol/L (p = 0.38). Results for the 6- and 24-month time points were similar to the 12-month results. Mean weight loss at 24 months of the study was not different among groups (p = 0.52). Serum calcium did not change significantly, and there were no cases of hypercalcemia or sustained hypercalciuria. CONCLUSIONS: Higher doses of vitamin D supplementation trend towards higher levels of 25OHD. Vitamin D replacement as high as 5,000 IU /day is safe and necessary in many patients to treat vitamin D deficiency following Roux-en-Y gastric bypass yet is still suboptimal in others.

Dyslipidemia can be controlled in diabetic as well as nondiabetic recipients after kidney transplant.

BACKGROUND: Patients with diabetes have been reported to have greater dyslipidemia after kidney transplant (KTX). Because postKTX management of diabetes has changed markedly since those reports, we hypothesized that lipids can be controlled as well in diabetic as in nondiabetic recipients. METHODS: We compared lipid levels up to 2 years after KTX (n=192) between diabetic and nondiabetic recipients. The cohort was subdivided into nondiabetic (nonDM-K; n=123), type 2 (DM2-K; n=33), or type 1 diabetes after KTX (DM1-K; n=14), or type 1 after kidney-pancreas transplant (DM1-KP; n=22). RESULTS: Mean age and body mass index of DM2-K were greater than the others (P<0.01), and diabetes groups had a higher pretransplant A1C than nonDM-K (P<0.001). After KTX, lipid levels were not higher in diabetic than in nondiabetic recipients, and did not increase in any group. Total and low-density lipoprotein cholesterol levels decreased in DM1-K (P<0.001), high-density lipoprotein levels decreased in DM1-KP (P=0.02), and triglyceride levels were unchanged after KTX for all groups. A1C improved in DM1-K and DM1-KP (P<0.0001). There was less improvement in lipid levels with tacrolimus-sirolimus immunosuppression than with other steroid-containing regimens (P<0.05). CONCLUSIONS: Multiple mechanisms may contribute to better lipid levels in both groups as well as the lack of difference between diabetic and nondiabetic recipients compared with what has been reported previously: greater use of and more effective lipid-lowering agents, no significant weight gain, no difference in renal function between groups, and better control of glucose in the diabetic group. Thus, overall, lipids can be controlled as well in diabetic as in nondiabetic KTX recipients.

Prevalence of vitamin D insufficiency and deficiency in morbidly obese patients: a comparison with non-obese controls.

BACKGROUND: Vitamin D deficiency is common in patients after bariatric surgery. However, obesity itself has also been associated with decreased vitamin D. The prevalence of vitamin D deficiency in obese persons has not previously been compared to non-obese controls when controlling for factors that could affect vitamin D status. METHODS: We evaluated 25 hydroxy vitamin D, iPTH, calcium, albumin, and creatinine in 41 patients undergoing Roux-en-Y gastric bypass. We then compared them to healthy non-obese controls matched for age, sex, race/ethnicity, and season of vitamin D measurement. RESULTS: Ninety percent of the pre-bariatric surgery patients had 25-OH-D levels <75 nmol/l, and 61% had 25-OH-D levels <50 nmol/l versus 32 and 12% in controls, respectively. Additionally, 49% of the pre-bariatric surgery patients had secondary hyperparathyroidism versus 2% of controls. These differences persisted after controlling for sunlight exposure and dietary intake of calcium and vitamin D. Mean calcium, corrected for albumin, and creatinine were not significantly different between the groups, but mean albumin levels were significantly lower among surgery patients. CONCLUSION: Vitamin D deficiency is common in obese patients at the time of bariatric surgery and is also accompanied by secondary hyperparathyroidism approximately half the time. These findings suggest that vitamin D deficiency after bariatric surgery is multifactorial and in part caused by preoperative vitamin D deficiency rather than postoperative malabsorption alone. In this study, increased vitamin D deficiency in obese persons cannot be explained by a difference in calcium/vitamin D intake or sunlight exposure.

Hepatitis-C prevalence in an urban native-American clinic: a prospective screening study.

BACKGROUND: Native-American populations are disproportionately burdened by chronic liver disease, and the prevalence of hepatitis C (HCV) in native Americans is unknown. PURPOSE: To determine the prevalence of hepatitis C in a local native-American population via a prospective screening study. PROCEDURES: Two-hundred-forty-three native Americans (161 females/82 males) using an urban clinic and representing > 30 tribes from across the United States were screened. Mean age was 41 +/- 1 years. Hepatitis-C screening was by anti-HCV with confirmation by HCV RNA. A questionnaire assessed potential risk factors for HCV. FINDINGS: Anti-HCV antibodies were found in 11.5% (95% CI: 7.5-15.5%). HCV RNA was present by polymerase chain reaction (PCR) in 8.6% (95% CI: 5.1-12.1%) and was more common in males [13.4% (95% CI: 6.0-20.8%)] than females [6.2% (95% CI: 2.5-9.9%)]. The most common potential risk factors for chronic HCV infection were intravenous (IV) drug or cocaine use (p < 0.0001), tattoos > 5 years old (p < 0.0001) and having a sexual partner with HCV (p = 0.0063). CONCLUSION: HCV prevalence is higher in an urban native-American clinic population than reported in the general U.S. population. Use of IV drugs is the most prevalent risk factor, but tattoos and sexual transmission may also be important.

Comparison of CT and dual-energy DEXA using a modified trunk compartment in the measurement of abdominal fat.

The quantification of abdominal fat is a marker of health risk. While dual-energy x-ray absorptiometry (DEXA) is easily applied, it measures overall fat, although abdominal fat may be a better indicator of health risk from obesity. We have evaluated whether a subcomponent of DEXA measurements correlates better with computed tomography (CT) for body fat than those traditionally used. Forty-seven healthy adults (22 M/25 F), aged 54.5+/-15.8 yr (mean+/-SD), with BMI of 27.1+/-4.6 kg/m2 participated in a cross-sectional study. Body fat was measured using abdominal CT and DEXA for total fat, trunk fat, and a modified trunk measurement that excludes the chest, termed "lower trunk," and compared. The coefficient of variation for DEXA measurements for trunk, lower trunk, and total body were 1.98, 3.12, and 0.85%, respectively. Mean DEXA for percentage fat ranged from 31.7% to 34.1% for trunk, lower trunk, and total body, compared to 54.2% for abdominal CT (p<0.003 for each pairwise comparison). Lower trunk, whole trunk, and total body DEXA measurements were not different. Measurement of subcomponents of fat content by DEXA is not superior to whole body measurements and remains consistently lower than measurements by CT.

Heel ultrasonography is not a good screening tool for bone loss after kidney and pancreas transplantation.

BACKGROUND: Solid organ transplant recipients, particularly simultaneous pancreas kidney recipients, are at high fracture risk. We tested whether quantitative ultrasonography (QUS) of the heel predicts bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) in solid organ transplant recipients. METHODS: Thirty-eight transplant recipients (22 Female/16 Male) were studied. Spine and hip BMD was measured with a Hologic DXA scanner. 'Stiffness' of the heel was measured with a Lunar Ultrasound densitometer and compared with BMD by DXA. Contributing factors to bone loss were also assessed. RESULTS: Mean age was 43.1 +/- 1.3 yr. Simultaneous pancreas-kidney, kidney, and pancreas alone transplant recipients were assessed. Mean time post-transplantation was 3.0 +/- 0.6 yr. Mean DXA spine T-score was -1.15 +/- 0.22 (mean +/- SEM) and hip T-score was -1.22 +/- 0.20. There was no difference in mean T-score between women and men at the hip or spine. Mean right heel stiffness T-score was -0.97 +/- 0.25. There was no correlation between QUS and DXA at either the hip or spine in women or men. QUS had a false negative rate for identifying osteopenia or osteoporosis of 17% compared with DXA. The false positive rate for identifying osteopenia was 61%. CONCLUSIONS: The QUS is an unacceptable tool for identifying those at risk for bone loss after kidney or pancreas transplantation.

Pancreas transplantation improves vascular disease in patients with type 1 diabetes.

OBJECTIVE: Pancreas transplantation (PTX) normalizes glucose and improves microvascular complications, but its impact on macrovascular disease is still debated. RESEARCH DESIGN AND METHODS: Carotid intima-media thickness (IMT), shown to correlate with cardiovascular disease (CVD) risk and events, was determined prospectively by ultrasonography in successful pancreas transplant recipients to evaluate the effect of PTX on CVD risk. Carotid IMT and CVD risk factors of pancreas transplant recipients (n = 25) were compared with three groups: individuals with type 1 diabetes without significant nephropathy (n = 20), nondiabetic kidney transplant recipients (n = 16), and normal control subjects (n = 32). Mean age of pancreas transplant recipients at the time of transplantation was 42.4 +/- 1.2 years (mean +/- SE) and duration of diabetes was 25.9 +/- 1.4 years. RESULTS: After PTX, HbA(1c) level (P < 0.0001) decreased to normal and, whereas creatinine level (P = 0.0002) decreased, it remained elevated compared with normal control subjects (P < 0.05). Blood pressure, BMI, fasting lipid levels, smoking frequency, and use of hypolipidemic agents were unchanged. Mean carotid IMT was increased in pancreas transplant candidates but decreased by 1.8 +/- 0.1 year after PTX (P = 0.0068), no longer different from that in normal control subjects or patients with type 1 diabetes. CONCLUSIONS: Carotid IMT improves after successful PTX within 2 years of the procedure, with normalization of HbA(1c) and improved renal function, independent of changes in lipid levels, BMI, blood pressure, smoking, or use of hypolipidemic agents. This study suggests that CVD risk, future events, and mortality should improve after PTX in the absence of other significant, untreated CVD risk factors.

Apolipoprotein E gene polymorphism alters lipids before pancreas transplantation.

BACKGROUND: Pancreas transplantation (PTX) improves lipids in patients with type 1 diabetes mellitus. However, there are patients who have persistent abnormal lipids or develop new hyperlipidemia despite PTX. One factor that may influence the lipid profile is apolipoprotein E (Apo E) genotype. Apo E polymorphism, particularly E2 and E4 alleles, increases the risk of dyslipidemia. Apo E2 has also been found to increase risk of diabetic nephropathy and so may be more prevalent in PTX candidates. METHODS: This study evaluated fasting-lipid profiles in type 1 diabetes patients who were pancreas transplant candidates to prospectively evaluate the impact of Apo E genotype on dyslipidemia before and after PTX. RESULTS: Presence of one or more E4 alleles resulted in higher triglycerides ( =0.0446), lower HDL ( =0.0247), and a higher cholesterol-to-HDL (C/H) ratio ( =0.0405) before PTX when compared with those with E3/3 genotype. After PTX, lipids improved so there was no longer a difference in fasting lipids between patients with an E4 allele and E3/3 genotype. Presence of an E2 allele had no significant impact on fasting lipids before or after PTX. CONCLUSIONS: Presence of an Apo E4 allele worsened HDL, triglycerides, and C/H ratio before PTX compared with those with E3/3 genotype, whereas the presence of an Apo E2 allele had no significant effect on lipids before or after PTX. Thus, Apo E4 has a larger impact than Apo E2 on fasting-lipid profile in PTX candidates, and Apo E gene polymorphism does not worsen lipid dyslipidemia after PTX, despite introduction of immunosuppressant medications known to cause dyslipidemia.

Carotid intima media thickness decreases after pancreas transplantation.

BACKGROUND: Pancreas transplantation (PTX) improves diabetic microvascular complications, but it is unknown whether PTX alters macrovascular disease. Carotid intima media thickness (IMT) has been shown to correlate with cardiovascular events, so this study was designed to evaluate changes in carotid IMT after PTX. METHODS: Four groups were studied: PTX candidates (n=60); successful PTX recipients (n=89; mean time since PTX=4.0+/-0.3 years); patients with type 1 diabetes but without nephropathy (n=20); and normal controls (n=32). Mean IMT and mean of maximum carotid IMT measurements (mean-max IMT), hemoglobin A1C, serum creatinine, body mass index (BMI), blood pressure, smoking status, use of hypolipidemic medications, and fasting lipids were determined in all groups. RESULTS: Age, gender distribution, and BMI were not different among the groups. Duration of diabetes was also equal between pre- and post-PTX groups. Mean and mean-max IMT were greatest pre-PTX and decreased after PTX (P<0.05) to a value that was not different from controls. Hemoglobin A1C and creatinine decreased, and high density lipoprotein (HDL) increased after PTX (P<0.05), but there were no significant differences in other lipids, BMI, use of lipid lowering agents, blood pressure, or smoking status. CONCLUSIONS: Carotid IMT is lower after PTX, suggesting a reduction in overall cardiovascular risk independent of changes in use of hypolipidemic agents, smoking, blood pressure, BMI, or lipids, except HDL. Improved carotid IMT after successful PTX predicts a reduction in future vascular disease events and suggests that the macrovascular disease of type 1 diabetes is at least partially reversible with improved glucose control.